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For: Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA. Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ 2007;14:275-85. [PMID: 16763620 DOI: 10.1038/sj.cdd.4401979] [Citation(s) in RCA: 192] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

For:	Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA. Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ 2007;14:275-85. [PMID: 16763620 DOI: 10.1038/sj.cdd.4401979] [Citation(s) in RCA: 192] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Number

Cited by Other Article(s)

Irshad I, Alqahtani SA, Ikejima K, Yu ML, Romero-Gomez M, Eslam M. Energy metabolism: An emerging therapeutic frontier in liver fibrosis. Ann Hepatol 2025;30:101896. [PMID: 40057035 DOI: 10.1016/j.aohep.2025.101896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 02/04/2025] [Indexed: 03/18/2025]

Sood S, Tiwari A, Sangwan J, Vohra M, Sinha NR, Tripathi R, Sangwan VS, Mohan RR. Role of epigenetics in corneal health and disease. Prog Retin Eye Res 2025;104:101318. [PMID: 39547455 PMCID: PMC11710990 DOI: 10.1016/j.preteyeres.2024.101318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 11/17/2024]

Su L, Bu J, Yu J, Jin M, Meng G, Zhu X. Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application. Clin Transl Med 2024;14:e70066. [PMID: 39462685 PMCID: PMC11513202 DOI: 10.1002/ctm2.70066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 09/30/2024] [Accepted: 10/08/2024] [Indexed: 10/29/2024] Open

Jiang L, Koh JHZ, Seah SHY, Dan YS, Wang Z, Chan X, Zhou L, Barathi VA, Hoang QV. Key role for inflammation-related signaling in the pathogenesis of myopia based on evidence from proteomics analysis. Sci Rep 2024;14:23486. [PMID: 39379387 PMCID: PMC11461836 DOI: 10.1038/s41598-024-67337-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 07/10/2024] [Indexed: 10/10/2024] Open

Affiliation(s)

Liqin Jiang Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore
James H Z Koh Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore
Sherlyn H Y Seah Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Yee Shan Dan Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore
Zhaoran Wang Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore
Xavier Chan Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore
Lei Zhou School of Optometry, Department of Applied Biology and Chemical Technology, Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Hong Kong, China Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong, China
Veluchamy Amutha Barathi Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Quan V Hoang Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, 20 College Rd, Singapore, 169856, Singapore. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Department of Ophthalmology, Columbia University, New York, NY, USA.

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Dong QQ, Yang Y, Tao H, Lu C, Yang JJ. m6A epitranscriptomic and epigenetic crosstalk in liver fibrosis: Special emphasis on DNA methylation and non-coding RNAs. Cell Signal 2024;122:111302. [PMID: 39025344 DOI: 10.1016/j.cellsig.2024.111302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/11/2024] [Accepted: 07/12/2024] [Indexed: 07/20/2024]

Yang M, Wang D, Wang X, Mei J, Gong Q. Role of Folate in Liver Diseases. Nutrients 2024;16:1872. [PMID: 38931227 PMCID: PMC11206401 DOI: 10.3390/nu16121872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/06/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open

Osna NA, Tikhanovich I, Ortega-Ribera M, Mueller S, Zheng C, Mueller J, Li S, Sakane S, Weber RCG, Kim HY, Lee W, Ganguly S, Kimura Y, Liu X, Dhar D, Diggle K, Brenner DA, Kisseleva T, Attal N, McKillop IH, Chokshi S, Mahato R, Rasineni K, Szabo G, Kharbanda KK. Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression. Biomolecules 2024;14:404. [PMID: 38672422 PMCID: PMC11048648 DOI: 10.3390/biom14040404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 03/20/2024] [Accepted: 03/24/2024] [Indexed: 04/28/2024] Open

Affiliation(s)

Natalia A. Osna Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68106, USA Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68106, USA
Irina Tikhanovich Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA;
Martí Ortega-Ribera Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; (M.O.-R.); (G.S.)
Sebastian Mueller Center for Alcohol Research, University of Heidelberg, 69120 Heidelberg, Germany; (S.M.); (C.Z.); (J.M.); (S.L.) Viscera AG Bauchmedizin, 83011 Bern, Switzerland
Chaowen Zheng Center for Alcohol Research, University of Heidelberg, 69120 Heidelberg, Germany; (S.M.); (C.Z.); (J.M.); (S.L.)
Johannes Mueller Center for Alcohol Research, University of Heidelberg, 69120 Heidelberg, Germany; (S.M.); (C.Z.); (J.M.); (S.L.)
Siyuan Li Center for Alcohol Research, University of Heidelberg, 69120 Heidelberg, Germany; (S.M.); (C.Z.); (J.M.); (S.L.)
Sadatsugu Sakane Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Raquel Carvalho Gontijo Weber Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Hyun Young Kim Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Wonseok Lee Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Souradipta Ganguly Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Yusuke Kimura Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Xiao Liu Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Debanjan Dhar Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.)
Karin Diggle Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
David A. Brenner Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; (S.S.); (R.C.G.W.); (H.Y.K.); (W.L.); (S.G.); (Y.K.); (X.L.); (D.D.); (K.D.); (D.A.B.) Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
Tatiana Kisseleva Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA;
Neha Attal Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA; (N.A.); (I.H.M.)
Iain H. McKillop Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA; (N.A.); (I.H.M.)
Shilpa Chokshi The Roger Williams Institute of Hepatology, Foundation for Liver Research, London SE59NT, UK; School of Microbial Sciences, King’s College, London SE59NT, UK
Ram Mahato Department of Pharmaceutical Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68106, USA;
Karuna Rasineni Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68106, USA;
Gyongyi Szabo Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; (M.O.-R.); (G.S.)
Kusum K. Kharbanda Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68106, USA Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68106, USA; Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA

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Zaidi MB, Khan F, Jameel F, Khan I, Musharraf SG, Salim A. Temporal and differential proteomic profile of molecular mediators associated with chronic and acute wound healing. Cell Biochem Funct 2024;42:e3946. [PMID: 38379227 DOI: 10.1002/cbf.3946] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 01/15/2024] [Accepted: 01/17/2024] [Indexed: 02/22/2024]

Abstract

The underlying pathophysiology of nonhealing chronic wounds is poorly understood due to the changes occurring at the gene level and the complexity arising in their proteomic profile. Here, we elucidated the temporal and differential profile of the normal and diabetic wound-healing mediators along with their interactions and associated pathways. Skin tissues corresponding to normal and diabetic wounds were isolated at Days 0, 3, 6, and 9 representing different healing phases. Temporal gene expression was analyzed by quantitative real-time PCR. Concurrently, differential protein patterns in the wound tissues were identified by Nano LC-ESI-TOF mass spectrometry and later confirmed by Western blot analysis. Gene ontology annotation, protein-protein interaction, and protein pathway analysis were performed using DAVID, PANTHER, and STRING bioinformatics resources. Uniquely identified proteins (complement C3, amyloid beta precursor protein, and cytoplasmic linker associated protein 2) in the diabetic wound tissue implied that these proteins are involved in the pathogenesis of diabetic wound. They exhibit enhanced catalytic activity, trigger pathways linked with inflammation, and negatively regulate wound healing. However, in the normal wound tissue, axin 1, chondroitin sulfate proteoglycan 4, and sphingosine-1-phosphate receptor were identified, which are involved in proliferation, angiogenesis, and remodeling. Our findings demonstrate the correlation between elevated gene expression of tumor necrosis factor-α, interleukin (IL)-1β, and identified mediators: aryl hydrocarbon receptor nuclear translocator, 5'-aminolevulinate synthase 2, and CXC-family, that inflicted an inflammatory response by activating downstream MAPK, JAK-STAT, and NF-κB pathways. Similarly, in normal wound tissue, the upregulated IL-4 and hepatocyte growth factor levels in conjunction with the identified proteins, serine/threonine-protein kinase mTOR and peroxisome proliferator-activated receptor gamma, played a significant role in the cellular response to platelet-derived growth factor stimulus, dermal epithelialization, and cell proliferation, processes associated with the repair mechanism. Furthermore, Western blot analysis indicated elevated levels of inflammatory markers and reduced levels of proliferative and angiogenic factors in the diabetic wound.

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Zuo C, Fan P, Yang Y, Hu C. MiR-488-3p facilitates wound healing through CYP1B1-mediated Wnt/β-catenin signaling pathway by targeting MeCP2. J Diabetes Investig 2024;15:145-158. [PMID: 37961023 PMCID: PMC10804895 DOI: 10.1111/jdi.14099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 09/15/2023] [Accepted: 09/28/2023] [Indexed: 11/15/2023] Open

Luo J, Zhu WC, Chen QX, Yang CF, Huang BJ, Zhang SJ. A prognostic model based on DNA methylation-related gene expression for predicting overall survival in hepatocellular carcinoma. Front Oncol 2024;13:1171932. [PMID: 38304027 PMCID: PMC10830715 DOI: 10.3389/fonc.2023.1171932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 12/27/2023] [Indexed: 02/03/2024] Open

Abstract

Background

Hepatocellular carcinoma (HCC) continues to increase in morbidity and mortality among all types of cancer. DNA methylation, an important epigenetic modification, is associated with cancer occurrence and progression. The objective of this study was to establish a model based on DNA methylation risk scores for identifying new potential therapeutic targets in HCC and preventing cancer progression.

Methods

Transcriptomic, clinical, and DNA methylation data on 374 tumor tissues and 50 adjacent normal tissues were downloaded from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma database. The gene expression profiles of the GSE54236 liver cancer dataset, which contains data on 161 liver tissue samples, were obtained from the Gene Expression Omnibus database. We analyzed the relationship between DNA methylation and gene expression levels after identifying the differentially methylated and expressed genes. Then, we developed and validated a risk score model based on the DNA methylation-driven genes. A tissue array consisting of 30 human hepatocellular carcinoma samples and adjacent normal tissues was used to assess the protein and mRNA expression levels of the marker genes by immunohistochemistry and qRT-PCR, respectively.

Results

Three methylation-related differential genes were identified in our study: GLS, MEX3B, and GNA14. The results revealed that their DNA methylation levels were negatively correlated with local gene expression regulation. The gene methylation levels correlated strongly with the prognosis of patients with liver cancer. This was confirmed by qRT-PCR and immunohistochemical verification of the expression of these genes or proteins in tumors and adjacent tissues. These results revealed the relationship between the level of relevant gene methylation and the prognosis of patients with liver cancer as well as the underlying cellular and biological mechanisms. This allows our gene signature to provide more accurate and appropriate predictions for clinical applications.

Conclusion

Through bioinformatics analysis and experimental validation, we obtained three DNA methylation marker: GLS, MEX3B, and GNA14. This helps to predict the prognosis and may be a potential therapeutic target for HCC patients.

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Song Y, Kim N, Heo J, Shum D, Heo T, Seo HR. Inhibition of DNMT3B expression in activated hepatic stellate cells overcomes chemoresistance in the tumor microenvironment of hepatocellular carcinoma. Sci Rep 2024;14:115. [PMID: 38168140 PMCID: PMC10761987 DOI: 10.1038/s41598-023-50680-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 12/22/2023] [Indexed: 01/05/2024] Open

Feng Y, Guo S, Zhao Y, Dong H, Qian J, Hu Y, Wu L, Jia Y, Zhao R. DNA 5mC and RNA m⁶A modification successively facilitates the initiation and perpetuation stages of HSC activation in liver fibrosis progression. Cell Death Differ 2023;30:1211-1220. [PMID: 36841889 PMCID: PMC10154415 DOI: 10.1038/s41418-023-01130-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 02/02/2023] [Accepted: 02/09/2023] [Indexed: 02/27/2023] Open

Affiliation(s)

Yue Feng MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, Jiangsu, PR China Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, PR China
Shihui Guo MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, Jiangsu, PR China Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, PR China
Yulan Zhao MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, Jiangsu, PR China Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, PR China
Haibo Dong Center for Translational Biomedical Research, UNCG, Kannapolis, NC, USA
Jiayu Qian Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, PR China
Yun Hu College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, PR China
Lei Wu MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, Jiangsu, PR China Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, PR China
Yimin Jia MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, Jiangsu, PR China Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, PR China
Ruqian Zhao MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, Jiangsu, PR China. Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, PR China.

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Yano N, Fedulov AV. Targeted DNA Demethylation: Vectors, Effectors and Perspectives. Biomedicines 2023;11:biomedicines11051334. [PMID: 37239005 DOI: 10.3390/biomedicines11051334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/21/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023] Open

Alpoim-Moreira J, Szóstek-Mioduchowska A, Słyszewska M, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts. Animals (Basel) 2023;13:ani13071212. [PMID: 37048467 PMCID: PMC10093662 DOI: 10.3390/ani13071212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/03/2023] [Accepted: 03/27/2023] [Indexed: 04/03/2023] Open

Effendi WI, Nagano T. Epigenetics Approaches toward Precision Medicine for Idiopathic Pulmonary Fibrosis: Focus on DNA Methylation. Biomedicines 2023;11:biomedicines11041047. [PMID: 37189665 DOI: 10.3390/biomedicines11041047] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 03/31/2023] Open

Distler JHW, Riemekasten G, Denton CP. The Exciting Future for Scleroderma. Rheum Dis Clin North Am 2023;49:445-462. [PMID: 37028846 DOI: 10.1016/j.rdc.2023.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]

Gauthier V, Kyriazi M, Nefla M, Pucino V, Raza K, Buckley CD, Alsaleh G. Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing. Front Immunol 2023;14:1137659. [PMID: 36926329 PMCID: PMC10011104 DOI: 10.3389/fimmu.2023.1137659] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023] Open

Affiliation(s)

Vincent Gauthier Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.,The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.,Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
Maria Kyriazi Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.,Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom
Meriam Nefla The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.,Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
Valentina Pucino The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.,Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
Karim Raza Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.,Department of Rheumatology, Sandwell and West, Birmingham Hospitals NHS Trust, Birmingham, United Kingdom
Christopher D Buckley The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.,Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
Ghada Alsaleh Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom.,The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United Kingdom

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Zheng J, Wang J, Qin X, Li K, Gao Q, Yang M, Liu H, Li S, Chang X, Sun Y. LncRNA HOTAIRM1 Involved in Nano NiO-Induced Pulmonary Fibrosis via Regulating PRKCB DNA Methylation-Mediated JNK/c-Jun Pathway. Toxicol Sci 2022;190:64-78. [PMID: 36066426 DOI: 10.1093/toxsci/kfac092] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open

Riemekasten G, Distler JH. A broad look into the future of systemic sclerosis. Ther Adv Musculoskelet Dis 2022;14:1759720X221109404. [PMID: 35966183 PMCID: PMC9373175 DOI: 10.1177/1759720x221109404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 06/07/2022] [Indexed: 11/28/2022] Open

Czaja AJ. Epigenetic Aspects and Prospects in Autoimmune Hepatitis. Front Immunol 2022;13:921765. [PMID: 35844554 PMCID: PMC9281562 DOI: 10.3389/fimmu.2022.921765] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 05/12/2022] [Indexed: 12/12/2022] Open

Abstract

The observed risk of autoimmune hepatitis exceeds its genetic risk, and epigenetic factors that alter gene expression without changing nucleotide sequence may help explain the disparity. Key objectives of this review are to describe the epigenetic modifications that affect gene expression, discuss how they can affect autoimmune hepatitis, and indicate prospects for improved management. Multiple hypo-methylated genes have been described in the CD4⁺ and CD19⁺ T lymphocytes of patients with autoimmune hepatitis, and the circulating micro-ribonucleic acids, miR-21 and miR-122, have correlated with laboratory and histological features of liver inflammation. Both epigenetic agents have also correlated inversely with the stage of liver fibrosis. The reduced hepatic concentration of miR-122 in cirrhosis suggests that its deficiency may de-repress the pro-fibrotic prolyl-4-hydroxylase subunit alpha-1 gene. Conversely, miR-155 is over-expressed in the liver tissue of patients with autoimmune hepatitis, and it may signify active immune-mediated liver injury. Different epigenetic findings have been described in diverse autoimmune and non-autoimmune liver diseases, and these changes may have disease-specificity. They may also be responses to environmental cues or heritable adaptations that distinguish the diseases. Advances in epigenetic editing and methods for blocking micro-ribonucleic acids have improved opportunities to prove causality and develop site-specific, therapeutic interventions. In conclusion, the role of epigenetics in affecting the risk, clinical phenotype, and outcome of autoimmune hepatitis is under-evaluated. Full definition of the epigenome of autoimmune hepatitis promises to enhance understanding of pathogenic mechanisms and satisfy the unmet clinical need to improve therapy for refractory disease.

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Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis. Acta Pharm Sin B 2022;12:2443-2461. [PMID: 35646543 PMCID: PMC9136578 DOI: 10.1016/j.apsb.2021.12.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 11/29/2021] [Accepted: 12/22/2021] [Indexed: 01/18/2023] Open

Habash NW, Sehrawat TS, Shah VH, Cao S. Epigenetics of alcohol-related liver diseases. JHEP REPORTS : INNOVATION IN HEPATOLOGY 2022;4:100466. [PMID: 35462859 PMCID: PMC9018389 DOI: 10.1016/j.jhepr.2022.100466] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 02/14/2022] [Accepted: 02/22/2022] [Indexed: 02/07/2023]

Nguyen VQ, You DG, Kim CH, Kwon S, Um W, Oh BH, An JY, Jeon J, Park JH. An anti-DR5 antibody-curcumin conjugate for the enhanced clearance of activated hepatic stellate cells. Int J Biol Macromol 2021;192:1231-1239. [PMID: 34626726 DOI: 10.1016/j.ijbiomac.2021.09.176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 09/23/2021] [Accepted: 09/24/2021] [Indexed: 10/20/2022]

Castillo-Castro C, Martagón-Rosado AJ, Ortiz-Lopez R, Garrido-Treviño LF, Villegas-Albo M, Bosques-Padilla FJ. Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome. World J Hepatol 2021;13:1494-1511. [PMID: 34904026 PMCID: PMC8637675 DOI: 10.4254/wjh.v13.i11.1494] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/06/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open

Königshofer P, Brusilovskaya K, Petrenko O, Hofer BS, Schwabl P, Trauner M, Reiberger T. Nuclear Receptors in Liver Fibrosis. Biochim Biophys Acta Mol Basis Dis 2021;1867:166235. [PMID: 34339839 DOI: 10.1016/j.bbadis.2021.166235] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 07/18/2021] [Accepted: 07/27/2021] [Indexed: 12/12/2022]

Affiliation(s)

Philipp Königshofer Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Ksenia Brusilovskaya Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Oleksandr Petrenko Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Benedikt Silvester Hofer Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Philipp Schwabl Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Michael Trauner Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Thomas Reiberger Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

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Alcaraz J, Ikemori R, Llorente A, Díaz-Valdivia N, Reguart N, Vizoso M. Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities. Cancers (Basel) 2021;13:cancers13153782. [PMID: 34359678 PMCID: PMC8345093 DOI: 10.3390/cancers13153782] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/23/2021] [Accepted: 07/24/2021] [Indexed: 12/21/2022] Open

Abstract

Simple Summary

Lung cancer is the leading cause of cancer death among both men and women, partly due to limited therapy responses. New avenues of knowledge are indicating that lung cancer cells do not form a tumor in isolation but rather obtain essential support from their surrounding host tissue rich in altered fibroblasts. Notably, there is growing evidence that tumor progression and even the current limited responses to therapies could be prevented by rescuing the normal behavior of fibroblasts, which are critical housekeepers of normal tissue function. For this purpose, it is key to improve our understanding of the molecular mechanisms driving the pathologic alterations of fibroblasts in cancer. This work provides a comprehensive review of the main molecular mechanisms involved in fibroblast transformation based on epigenetic reprogramming, and summarizes emerging therapeutic approaches to prevent or overcome the pathologic effects of tumor-associated fibroblasts.

Abstract

Lung cancer is the leading cause of cancer-related death worldwide. The desmoplastic stroma of lung cancer and other solid tumors is rich in tumor-associated fibroblasts (TAFs) exhibiting an activated/myofibroblast-like phenotype. There is growing awareness that TAFs support key steps of tumor progression and are epigenetically reprogrammed compared to healthy fibroblasts. Although the mechanisms underlying such epigenetic reprogramming are incompletely understood, there is increasing evidence that they involve interactions with either cancer cells, pro-fibrotic cytokines such as TGF-β, the stiffening of the surrounding extracellular matrix, smoking cigarette particles and other environmental cues. These aberrant interactions elicit a global DNA hypomethylation and a selective transcriptional repression through hypermethylation of the TGF-β transcription factor SMAD3 in lung TAFs. Likewise, similar DNA methylation changes have been reported in TAFs from other cancer types, as well as histone core modifications and altered microRNA expression. In this review we summarize the evidence of the epigenetic reprogramming of TAFs, how this reprogramming contributes to the acquisition and maintenance of a tumor-promoting phenotype, and how it provides novel venues for therapeutic intervention, with a special focus on lung TAFs.

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Shi CX, Wang Y, Jiao FZ, Chen Q, Cao P, Pei MH, Zhang LY, Guo J, Deng W, Wang LW, Gong ZJ. Epigenetic Regulation of Hepatic Stellate Cell Activation and Macrophage in Chronic Liver Inflammation. Front Physiol 2021;12:683526. [PMID: 34276405 PMCID: PMC8281248 DOI: 10.3389/fphys.2021.683526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 06/03/2021] [Indexed: 11/13/2022] Open

Wang F, Malnassy G, Qiu W. The Epigenetic Regulation of Microenvironment in Hepatocellular Carcinoma. Front Oncol 2021;11:653037. [PMID: 33791228 PMCID: PMC8005717 DOI: 10.3389/fonc.2021.653037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 02/22/2021] [Indexed: 12/11/2022] Open

Histone deacetylase inhibitor givinostat alleviates liver fibrosis by regulating hepatic stellate cell activation. Mol Med Rep 2021;23:305. [PMID: 33649839 PMCID: PMC7974418 DOI: 10.3892/mmr.2021.11944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 01/08/2021] [Indexed: 12/13/2022] Open

Ganguly N, Chakrabarti S. Role of long non‑coding RNAs and related epigenetic mechanisms in liver fibrosis (Review). Int J Mol Med 2021;47:23. [PMID: 33495817 PMCID: PMC7846421 DOI: 10.3892/ijmm.2021.4856] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 10/29/2020] [Indexed: 02/07/2023] Open

Emerging physiological and pathological roles of MeCP2 in non-neurological systems. Arch Biochem Biophys 2021;700:108768. [PMID: 33485848 DOI: 10.1016/j.abb.2021.108768] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 01/08/2021] [Accepted: 01/14/2021] [Indexed: 02/08/2023]

Cui Z, Huang N, Liu L, Li X, Li G, Chen Y, Wu Q, Zhang J, Long S, Wang M, Sun F, Shi Y, Pan Q. Dynamic analysis of m6A methylation spectroscopy during progression and reversal of hepatic fibrosis. Epigenomics 2020;12:1707-1723. [PMID: 33174480 DOI: 10.2217/epi-2019-0365] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open

Hyun J, Jung Y. DNA Methylation in Nonalcoholic Fatty Liver Disease. Int J Mol Sci 2020;21:ijms21218138. [PMID: 33143364 PMCID: PMC7662478 DOI: 10.3390/ijms21218138] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 10/28/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022] Open

Claveria-Cabello A, Colyn L, Arechederra M, Urman JM, Berasain C, Avila MA, Fernandez-Barrena MG. Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? Cells 2020;9:cells9102321. [PMID: 33086678 PMCID: PMC7589994 DOI: 10.3390/cells9102321] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/15/2020] [Accepted: 10/17/2020] [Indexed: 12/13/2022] Open

Affiliation(s)

Alex Claveria-Cabello Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (A.C.-C.); (L.C.); (M.A.); (C.B.)
Leticia Colyn Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (A.C.-C.); (L.C.); (M.A.); (C.B.)
Maria Arechederra Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (A.C.-C.); (L.C.); (M.A.); (C.B.) National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain;
Jesus M. Urman IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain; Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, 31008 Pamplona, Spain
Carmen Berasain Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (A.C.-C.); (L.C.); (M.A.); (C.B.) National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain;
Matias A. Avila Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (A.C.-C.); (L.C.); (M.A.); (C.B.) National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain; Correspondence: (M.A.A.); (M.G.F.-B.); Tel.: +34-94-819-4700 (M.A.A.); +34-94-819-4700 (M.G.F.-B.)
Maite G. Fernandez-Barrena Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (A.C.-C.); (L.C.); (M.A.); (C.B.) National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain; Correspondence: (M.A.A.); (M.G.F.-B.); Tel.: +34-94-819-4700 (M.A.A.); +34-94-819-4700 (M.G.F.-B.)

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Asif S, Morrow NM, Mulvihill EE, Kim KH. Understanding Dietary Intervention-Mediated Epigenetic Modifications in Metabolic Diseases. Front Genet 2020;11:590369. [PMID: 33193730 PMCID: PMC7593700 DOI: 10.3389/fgene.2020.590369] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 09/21/2020] [Indexed: 12/12/2022] Open

Blum KA, Gupta S, Tickoo SK, Chan TA, Russo P, Motzer RJ, Karam JA, Hakimi AA. Sarcomatoid renal cell carcinoma: biology, natural history and management. Nat Rev Urol 2020;17:659-678. [PMID: 33051619 PMCID: PMC7551522 DOI: 10.1038/s41585-020-00382-9] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2020] [Indexed: 12/24/2022]

Abstract

Sarcomatoid dedifferentiation is an uncommon feature that can occur in most histological subtypes of renal cell carcinomas (RCCs) and carries a decidedly poor prognosis. Historically, conventional treatments for sarcomatoid RCCs (sRCCs) have shown little efficacy, and median survival is commonly 6–13 months. Despite being first described in 1968, the mechanisms driving sarcomatoid dedifferentiation remain poorly understood, and information and treatment options available to physicians and patients are limited. When diagnosed at an early stage, surgical intervention remains the treatment of choice. However, preoperative identification through routine imaging or biopsy is unreliable and most patients present with advanced disease and systemic symptoms. For these patients, the role of cytoreductive nephrectomy is disputed. The expansion of immunotherapies approved for RCCs has generated a search for biomarkers that might be indicative of treatment response in sRCCs, although a proven effective systemic agent remains elusive. PDL1 expression is increased in sarcomatoid dedifferentiated renal tumours, which suggests that patients with sRCCs could benefit from PD1 and/or PDL1 immune checkpoint blockade therapy. Treatment outcomes for sarcomatoid tumours have remained relatively consistent compared with other RCCs, but further investigation of the tumour–immune cell microenvironment might yield insights into further therapeutic possibilities.

In this Review, Blum et al. summarize the current knowledge on sarcomatoid renal cell carcinoma, a diagnosis characterized by the presence of sarcomatoid dedifferentiation and a poor prognosis. They discuss the origin, presentation, molecular biology and treatment of this disease.

Sarcomatoid dedifferentiation is not considered to be a unique histological subtype of renal cell carcinomas (RCCs); rather, it can be present within any subtype of RCCs.

Sarcomatoid dedifferentiation appears in ~4% of all RCCs, but is present in ~20% of all metastatic RCCs. According to WHO guidelines, any RCC with sarcomatoid dedifferentiation is a WHO–International Society of Urological Pathology grade 4 lesion.

Sarcomatoid dedifferentiation is often heterogeneously present within RCCs, making routine imaging and biopsy unreliable for preoperative detection. Surgical resection for localized disease is the standard of care, with subsequent close monitoring of patients following surgery.

In patients with metastatic disease, conventional therapies such as surgery and systemic agents have been ineffective and overall 5-year survival remains at 23.5–33%.

Previous genomic analyses have failed to identify definitive mutational drivers of disease. However, sarcomatoid RCCs (sRCCs) have been shown to have higher PD1 and PDL1 expression than other subtypes of RCCs. Newer combinations of immune checkpoint inhibitor immunotherapies could yield improved responses and outcomes.

Studies investigating sRCCs are limited by patient numbers owing to the low incidence of sRCCs and their advanced stage at presentation. Multi-institutional efforts to establish a consensus on treatment recommendations based on highly powered data are essential.

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Targeting chromatin dysregulation in organ fibrosis. Cytokine Growth Factor Rev 2020;57:64-72. [PMID: 32900600 DOI: 10.1016/j.cytogfr.2020.08.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 08/24/2020] [Accepted: 08/25/2020] [Indexed: 12/12/2022]

Li X, Li X, He S, Zhao M. MeCP2-421-mediated RPE epithelial-mesenchymal transition and its relevance to the pathogenesis of proliferative vitreoretinopathy. J Cell Mol Med 2020;24:9420-9427. [PMID: 32638535 PMCID: PMC7417696 DOI: 10.1111/jcmm.15602] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 06/13/2020] [Indexed: 12/17/2022] Open

Hydralazine Sensitizes to the Antifibrotic Effect of 5-Aza-2'-deoxycytidine in Hepatic Stellate Cells. BIOLOGY 2020;9:biology9060117. [PMID: 32503264 PMCID: PMC7345531 DOI: 10.3390/biology9060117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/21/2020] [Accepted: 05/27/2020] [Indexed: 11/17/2022]

Abstract

BACKGROUND

Hepatic stellate cell (HSC) activation is essential for the development of liver fibrosis. Epigenetic machinery, such as DNA methylation, is largely involved in the regulation of gene expression during HSC activation. Although the pharmacological DNA demethylation of HSC using 5-aza-2'-deoxycytidine (5-aza-dC) yielded an antifibrotic effect, this drug has been reported to induce excessive cytotoxicity at a high dose. Hydralazine (HDZ), an antihypertensive agent, also exhibits non-nucleoside demethylating activity. However, the effect of HDZ on HSC activation remains unclear. In this study, we performed a combined treatment with 5-aza-dC and HDZ to obtain an enhanced antifibrotic effect with lower cytotoxicity.

METHODS

HSC-T6 cells were used as a rat HSC cell line in this study. The cells were cultivated together with 1 µM 5-Aza-dC and/or 10 µg/mL of HDZ, which were refreshed every 24 h until the 96 h treatment ended. Cell proliferation was measured using the WST-1 assay. The mRNA expression levels of peptidylprolyl isomerase A (Ppia), an internal control gene, collagen type I alpha 1 (Cola1), RAS protein activator like 1 (Rasal1), and phosphatase and tensin homolog deleted from chromosome 10 (Pten) were analyzed using quantitative reverse transcription polymerase chain reaction.

RESULTS

The percentage cell viability with 5-aza-dC, HDZ, and combined treatment vs. the vehicle-only control was 101.4 ± 2.5, 95.2 ± 5.7, and 79.2 ± 0.7 (p < 0.01 for 5-aza-dC and p < 0.01 for HDZ), respectively, in the 48 h treatment, and 52.4 ± 5.6, 65.9 ± 3.4, and 29.9 ± 1.3 (p < 0.01 for 5-aza-dC and p < 0.01 for HDZ), respectively, in the 96 h treatment. 5-Aza-dC and the combined treatment markedly decreased Cola1 mRNA levels. Accordingly, the expression levels of Rasal1 and Pten, which are antifibrotic genes, were increased by treatment after the 5-aza-dC and combined treatments. Moreover, single treatment with HDZ did not affect the expression levels of Cola1, Rasal1, or Pten. These results suggest that HDZ sensitizes to the antifibrotic effect of 5-aza-dC in HSC-T6 cells. The molecular mechanism underlying the sensitization to the antifibrotic effect of 5-aza-dC by HDZ remains to be elucidated. The expression levels of rat equilibrative nucleoside transporter genes (rEnt1, rEnt2, and rEnt3) were not affected by HDZ in this study.

CONCLUSIONS

Further confirmation using primary HSCs and in vivo animal models is desirable, but combined treatment with 5-aza-dC and HDZ may be an effective therapy for liver fibrosis without severe adverse effects.

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Chen L, Huang W, Wang L, Zhang Z, Zhang F, Zheng S, Kong D. The effects of epigenetic modification on the occurrence and progression of liver diseases and the involved mechanism. Expert Rev Gastroenterol Hepatol 2020;14:259-270. [PMID: 32124651 DOI: 10.1080/17474124.2020.1736042] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Tillotson R, Bird A. The Molecular Basis of MeCP2 Function in the Brain. J Mol Biol 2020;432:1602-1623. [PMID: 31629770 DOI: 10.1016/j.jmb.2019.10.004] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/04/2019] [Accepted: 10/05/2019] [Indexed: 12/14/2022]

Wang M, Ye Q, Mao D, Li H. Research Progress in Liver-Regenerating Microenvironment and DNA Methylation in Hepatocellular Carcinoma: The Role of Traditional Chinese Medicine. Med Sci Monit 2020;26:e920310. [PMID: 32144233 PMCID: PMC7077739 DOI: 10.12659/msm.920310] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open

Distler JHW, Györfi AH, Ramanujam M, Whitfield ML, Königshoff M, Lafyatis R. Shared and distinct mechanisms of fibrosis. Nat Rev Rheumatol 2019;15:705-730. [PMID: 31712723 DOI: 10.1038/s41584-019-0322-7] [Citation(s) in RCA: 387] [Impact Index Per Article: 64.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2019] [Indexed: 02/07/2023]

Ikemori R, Gabasa M, Duch P, Vizoso M, Bragado P, Arshakyan M, Luis IC, Marín A, Morán S, Castro M, Fuster G, Gea-Sorli S, Jauset T, Soucek L, Montuenga LM, Esteller M, Monsó E, Peinado VI, Gascon P, Fillat C, Hilberg F, Reguart N, Alcaraz J. Epigenetic SMAD3 Repression in Tumor-Associated Fibroblasts Impairs Fibrosis and Response to the Antifibrotic Drug Nintedanib in Lung Squamous Cell Carcinoma. Cancer Res 2019;80:276-290. [PMID: 31694906 DOI: 10.1158/0008-5472.can-19-0637] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 09/13/2019] [Accepted: 10/29/2019] [Indexed: 11/16/2022]

Abstract

The tumor-promoting fibrotic stroma rich in tumor-associated fibroblasts (TAF) is drawing increased therapeutic attention. Intriguingly, a trial with the antifibrotic drug nintedanib in non-small cell lung cancer reported clinical benefits in adenocarcinoma (ADC) but not squamous cell carcinoma (SCC), even though the stroma is fibrotic in both histotypes. Likewise, we reported that nintedanib inhibited the tumor-promoting fibrotic phenotype of TAFs selectively in ADC. Here we show that tumor fibrosis is actually higher in ADC-TAFs than SCC-TAFs in vitro and patient samples. Mechanistically, the reduced fibrosis and nintedanib response of SCC-TAFs was associated with increased promoter methylation of the profibrotic TGFβ transcription factor SMAD3 compared with ADC-TAFs, which elicited a compensatory increase in TGFβ1/SMAD2 activation. Consistently, forcing global DNA demethylation of SCC-TAFs with 5-AZA rescued TGFβ1/SMAD3 activation, whereas genetic downregulation of SMAD3 in ADC-TAFs and control fibroblasts increased TGFβ1/SMAD2 activation, and reduced their fibrotic phenotype and antitumor responses to nintedanib in vitro and in vivo. Our results also support that smoking and/or the anatomic location of SCC in the proximal airways, which are more exposed to cigarette smoke particles, may prime SCC-TAFs to stronger SMAD3 epigenetic repression, because cigarette smoke condensate selectively increased SMAD3 promoter methylation. Our results unveil that the histotype-specific regulation of tumor fibrosis in lung cancer is mediated through differential SMAD3 promoter methylation in TAFs and provide new mechanistic insights on the selective poor response of SCC-TAFs to nintedanib. Moreover, our findings support that patients with ADC may be more responsive to antifibrotic drugs targeting their stromal TGFβ1/SMAD3 activation. SIGNIFICANCE: This study implicates the selective epigenetic repression of SMAD3 in SCC-TAFs in the clinical failure of nintedanib in SCC and supports that patients with ADC may benefit from antifibrotic drugs targeting stromal TGFβ1/SMAD3.

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Affiliation(s)

Rafael Ikemori Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Marta Gabasa Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Paula Duch Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Miguel Vizoso Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands
Paloma Bragado Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Department of Medicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Marselina Arshakyan Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Iuliana-Cristiana Luis Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Albert Marín Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Sebastian Morán Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain
Manuel Castro Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain
Gemma Fuster Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Department of Medicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain
Sabrina Gea-Sorli Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
Toni Jauset Vall d'Hebron Institute of Oncology (VHIO), Edifici Cellex, Hospital Vall d'Hebrón, Barcelona, Spain
Laura Soucek Vall d'Hebron Institute of Oncology (VHIO), Edifici Cellex, Hospital Vall d'Hebrón, Barcelona, Spain.,Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.,Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain
Luis M Montuenga Program in Solid Tumors, Center for Applied Medical Research Institution (CIMA), University of Navarra, Pamplona, Spain.,Centro de Investigación Biomedica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Manel Esteller Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain.,Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.,Centro de Investigación Biomedica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.,Physiological Sciences Department, School of Medicine and Health Sciences, Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, Spain
Eduard Monsó Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.,Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain
Victor Ivo Peinado Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
Pere Gascon Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Department of Medicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.,Medical Oncology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Cristina Fillat Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Department of Medicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
Frank Hilberg Boehringer Ingelheim Austria RCV GmbH & Co KG, Vienna, Austria
Noemí Reguart Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Medical Oncology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Jordi Alcaraz Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain. .,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.,Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), Barcelona, Spain

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Moran-Salvador E, Garcia-Macia M, Sivaharan A, Sabater L, Zaki MY, Oakley F, Knox A, Page A, Luli S, Mann J, Mann DA. Fibrogenic Activity of MECP2 Is Regulated by Phosphorylation in Hepatic Stellate Cells. Gastroenterology 2019;157:1398-1412.e9. [PMID: 31352003 PMCID: PMC6853276 DOI: 10.1053/j.gastro.2019.07.029] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 07/12/2019] [Accepted: 07/17/2019] [Indexed: 12/19/2022]

Abstract

BACKGROUND & AIMS

Methyl-CpG binding protein 2, MECP2, which binds to methylated regions of DNA to regulate transcription, is expressed by hepatic stellate cells (HSCs) and is required for development of liver fibrosis in mice. We investigated the effects of MECP2 deletion from HSCs on their transcriptome and of phosphorylation of MECP2 on HSC phenotype and liver fibrosis.

METHODS

We isolated HSCs from Mecp2^-/y mice and wild-type (control) mice. HSCs were activated in culture and used in array analyses of messenger RNAs and long noncoding RNAs. Kyoto Encyclopedia of Genes and Genomes pathway analyses identified pathways regulated by MECP2. We studied mice that expressed a mutated form of Mecp2 that encodes the S80A substitution, MECP2S80, causing loss of MECP2 phosphorylation at serine 80. Liver fibrosis was induced in these mice by administration of carbon tetrachloride, and liver tissues and HSCs were collected and analyzed.

RESULTS

MECP2 deletion altered expression of 284 messenger RNAs and 244 long noncoding RNAs, including those that regulate DNA replication; are members of the minichromosome maintenance protein complex family; or encode CDC7, HAS2, DNA2 (a DNA helicase), or RPA2 (a protein that binds single-stranded DNA). We found that MECP2 regulates the DNA repair Fanconi anemia pathway in HSCs. Phosphorylation of MECP2S80 and its putative kinase, HAS2, were induced during transdifferentiation of HSCs. HSCs from MECP2S80 mice had reduced proliferation, and livers from these mice had reduced fibrosis after carbon tetrachloride administration.

CONCLUSIONS

In studies of mice with disruption of Mecp2 or that expressed a form of MECP2 that is not phosphorylated at S80, we found phosphorylation of MECP2 to be required for HSC proliferation and induction of fibrosis. In HSCs, MECP2 regulates expression of genes required for DNA replication and repair. Strategies to inhibit MECP2 phosphorylation at S80 might be developed for treatment of liver fibrosis.

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Moscoso CG, Steer CJ. "Let my liver rather heat with wine" - a review of hepatic fibrosis pathophysiology and emerging therapeutics. Hepat Med 2019;11:109-129. [PMID: 31565001 PMCID: PMC6731525 DOI: 10.2147/hmer.s213397] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 08/17/2019] [Indexed: 12/12/2022] Open

Abstract

Cirrhosis is characterized by extensive hepatic fibrosis, and it is the 14th leading cause of death worldwide. Numerous contributing conditions have been implicated in its development, including infectious etiologies, medication overdose or adverse effects, ingestible toxins, autoimmunity, hemochromatosis, Wilson’s disease and primary biliary cholangitis to list a few. It is associated with portal hypertension and its stigmata (varices, ascites, hepatic encephalopathy, combined coagulopathy and thrombophilia), and it is a major risk factor for hepatocellular carcinoma. Currently, orthotopic liver transplantation has been the only curative modality to treat cirrhosis, and the scarcity of donors results in many people waiting years for a transplant. Identification of novel targets for pharmacologic therapy through elucidation of key mechanistic components to induce fibrosis reversal is the subject of intense research. Development of robust models of hepatic fibrosis to faithfully characterize the interplay between activated hepatic stellate cells (the principal fibrogenic contributor to fibrosis initiation and perpetuation), hepatocytes and extracellular matrix components has the potential to identify critical components and mechanisms that can be exploited for targeted treatment. In this review, we will highlight key cellular pathways involved in the pathophysiology of fibrosis from extracellular ligands, effectors and receptors, to nuclear receptors, epigenetic mechanisms, energy homeostasis and cytokines. Further, molecular pathways of hepatic stellate cell deactivation are discussed, including apoptosis, senescence and reversal or transdifferentiation to an inactivated state resembling quiescence. Lastly, clinical evidence of fibrosis reversal induced by biologics and small molecules is summarized, current compounds under clinical trials are described and efforts for treatment of hepatic fibrosis with mesenchymal stem cells are highlighted. An enhanced understanding of the rich tapestry of cellular processes identified in the initiation, perpetuation and resolution of hepatic fibrosis, driven principally through phenotypic switching of hepatic stellate cells, should lead to a breakthrough in potential therapeutic modalities.

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Bian E, Chen X, Xu Y, Ji X, Cheng M, Wang H, Fang Z, Zhao B. A central role for MeCP2 in the epigenetic repression of miR-200c during epithelial-to-mesenchymal transition of glioma. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2019;38:366. [PMID: 31429770 PMCID: PMC6702741 DOI: 10.1186/s13046-019-1341-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 07/24/2019] [Indexed: 02/07/2023]

Affiliation(s)

Erbao Bian Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, 230601, Anhui Province, China.,Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China
Xueran Chen Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China
Yadi Xu Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, 230601, Anhui Province, China.,Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China
Xinghu Ji Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, 230601, Anhui Province, China.,Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China
Meng Cheng Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, 230601, Anhui Province, China.,Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China
Hongliang Wang Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, 230601, Anhui Province, China.,Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China
Zhiyou Fang Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, No. 350, Shushan Hu Road, Hefei, 230031, Anhui, China.
Bing Zhao Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, 230601, Anhui Province, China. .,Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China.

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Jorgensen BG, Ro S. Role of DNA Methylation in the Development and Differentiation of Intestinal Epithelial Cells and Smooth Muscle Cells. J Neurogastroenterol Motil 2019;25:377-386. [PMID: 31327220 PMCID: PMC6657918 DOI: 10.5056/jnm19077] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 05/27/2019] [Indexed: 12/15/2022] Open

Fu X, Li C, Liu Q, McMillin KW. GROWTH AND DEVELOPMENT SYMPOSIUM: STEM AND PROGENITOR CELLS IN ANIMAL GROWTH: The regulation of beef quality by resident progenitor cells1. J Anim Sci 2019;97:2658-2673. [PMID: 30982893 PMCID: PMC6541817 DOI: 10.1093/jas/skz111] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 04/01/2019] [Indexed: 12/11/2022] Open

Barcena-Varela M, Colyn L, Fernandez-Barrena MG. Epigenetic Mechanisms in Hepatic Stellate Cell Activation During Liver Fibrosis and Carcinogenesis. Int J Mol Sci 2019;20:E2507. [PMID: 31117267 PMCID: PMC6566358 DOI: 10.3390/ijms20102507] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 05/17/2019] [Accepted: 05/19/2019] [Indexed: 02/06/2023] Open