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Wang Y, Wu W, Xu Y, Wu C, Han Q, Lu T, Zhang H, Jiao L, Zhang Y, Liu B, Yu XY, Li Y. Ncl liquid-liquid phase separation and SUMOylation mediate the stabilization of HIF-1α expression and promote pyroptosis in ischemic hindlimb. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167706. [PMID: 39933290 DOI: 10.1016/j.bbadis.2025.167706] [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: 07/06/2024] [Revised: 01/02/2025] [Accepted: 02/03/2025] [Indexed: 02/13/2025]
Abstract
Liquid-liquid phase separation (LLPS) has emerged as a flexible intracellular compartment that modulates various pathological processes. Hypoxia-inducible factor-1α (HIF-1α) has been shown to play an essential role in inflammation after ischemic injury. However, the mechanisms underlying HIF-1α-induced inflammation in ischemic diseases have not been defined. This study found that HIF-1α mediated the progression of ischemia-induced muscle injury. After ischemic injury, SUMO1 is upregulated and rapidly activates NLRP3 inflammasome through the upregulation of HIF-1α, leading to enhanced inflammation and pyroptosis. Co-IP revealed an interaction between SUMO1 and HIF-1α and SUMOylation of HIF-1α at K477. Moreover, we demonstrated the important role of dynamic phase separation of Nucleolin (Ncl) in regulating HIF-1α mRNA stability through fluorescence recovery after photobleach (FRAP) analysis. The stability of HIF-1α is regulated by Ncl liquid-liquid phase separation and SUMOylation in ischemia-induced hindlimb injury. HIF-1α can promote the expression of NLRP3 and other inflammation-related molecules, leading to pyroptosis, suggesting that Ncl/LLPS/HIF-1α or SUMO1/HIF-1α pathway may be a new target for the treatment of inflammation in ischemic diseases. Although previous studies have found that HIF-1α is able to promote the expression of target genes after hypoxia, and these genes are used to maintain the stability of the intracellular environment to adapt to hypoxia. We found that HIF-1α is involved in the activation process of NLRP3 inflammasomes after hind limb ischemia, which enriches our understanding of the biological role of HIF-1α.
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Affiliation(s)
- Yanli Wang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Weiliang Wu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Yan Xu
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China
| | - Chengjie Wu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Qingfang Han
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Tonggan Lu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Huiling Zhang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Lijuan Jiao
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Yu Zhang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China
| | - Bin Liu
- Department of Cardiology, the Second Hospital of Jilin University, Changchun, Jilin 130041, PR China
| | - Xi-Yong Yu
- NMPA Key Laboratory for Clinical Research and Evaluation of Drug for Thoracic Diseases, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, PR China
| | - Yangxin Li
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China.
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Sonallya T, Juhász T, Szigyártó IC, Ilyés K, Singh P, Khamari D, Buzás EI, Varga Z, Beke-Somfai T. Categorizing interaction modes of antimicrobial peptides with extracellular vesicles: Disruption, membrane trespassing, and clearance of the protein corona. J Colloid Interface Sci 2025; 679:496-509. [PMID: 39378685 DOI: 10.1016/j.jcis.2024.09.244] [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: 05/04/2024] [Revised: 08/21/2024] [Accepted: 09/29/2024] [Indexed: 10/10/2024]
Abstract
Host antimicrobial peptides (AMPs) and extracellular vesicles (EVs) are known to play important roles as part of the immune system, from antimicrobial actions to immune regulation. Recent results also demonstrate that EVs could serve as carriers for AMPs. Related, it was shown that some AMPs can remove the protein corona (PC), the externally adsorbed layer of proteins, from EVs which can be exploited for subtractive proteomics strategies. The interaction of these compounds is thus interesting for multiple reasons from better insight to natural processes to direct applications in EV-based bioengineering. However, we have only limited information on the various ways these species may interact with each other. To reach a broader overview, here we selected twenty-six AMPs, including cell-penetrating peptides (CPPs), and investigated their interactions with red blood cell-derived vesicles (REVs). For this, we employed a complex lipid biophysics including linearly polarized light spectroscopy, flow cytometry, nanoparticle tracking analysis, electron microscopy and also zeta-potential measurements. This enabled the categorization of these peptides into distinct groups. At specific low concentrations, peptides such as LL-37 and lasioglossin-III were effective in PC elimination with minimal disruption of the membrane. In contrast, AMPs like KLA, bradykinin, histatin-5, and most of the tested CPPs (e.g. octa-arginine, penetratin, and buforin II), demonstrate cell-penetrating mechanisms as they could sustain large peptide concentrations with minimal membrane damage. The systematic overview presented here shows the potential mechanism of how AMPs and EVs could interact in vivo, and also how certain peptides may be employed to manipulate EVs for specific applications.
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Affiliation(s)
- Tasvilla Sonallya
- Biomolecular Self-assembly Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest H-1117, Magyar Tudósok Körútja 2, Hungary; Hevesy György PhD School of Chemistry, ELTE Eötvös Loránd University, Budapest H-1117, Pázmány Péter Sétány 1/A, Hungary
| | - Tünde Juhász
- Biomolecular Self-assembly Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest H-1117, Magyar Tudósok Körútja 2, Hungary
| | - Imola Cs Szigyártó
- Biomolecular Self-assembly Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest H-1117, Magyar Tudósok Körútja 2, Hungary
| | - Kinga Ilyés
- Hevesy György PhD School of Chemistry, ELTE Eötvös Loránd University, Budapest H-1117, Pázmány Péter Sétány 1/A, Hungary; Biological Nanochemistry Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest H-1117, Magyar Tudósok Körútja 2, Hungary
| | - Priyanka Singh
- Biomolecular Self-assembly Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest H-1117, Magyar Tudósok Körútja 2, Hungary
| | - Delaram Khamari
- Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary
| | - Edit I Buzás
- Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary; HCEMM Extracellular Vesicle Research Group, Semmelweis University, H-1089 Budapest, Nagyvárad tér 4, Hungary; HUN-REN-SU Translational Extracellular Vesicle Research Group, H-1089 Budapest, Nagyvárad tér 4, Hungary
| | - Zoltán Varga
- Biological Nanochemistry Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest H-1117, Magyar Tudósok Körútja 2, Hungary; Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest 1111, Hungary
| | - Tamás Beke-Somfai
- Biomolecular Self-assembly Research Group, Institute of Materials and Environmental Chemistry, HUN-REN Research Centre for Natural Sciences, Budapest H-1117, Magyar Tudósok Körútja 2, Hungary.
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Sun D, Xie C, Zhao Y, Liao J, Li S, Zhang Y, Wang D, Hua K, Gu Y, Du J, Huang G, Huang J. The gut microbiota-bile acid axis in cholestatic liver disease. Mol Med 2024; 30:104. [PMID: 39030473 PMCID: PMC11265038 DOI: 10.1186/s10020-024-00830-x] [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: 03/04/2024] [Accepted: 05/07/2024] [Indexed: 07/21/2024] Open
Abstract
Cholestatic liver diseases (CLD) are characterized by impaired normal bile flow, culminating in excessive accumulation of toxic bile acids. The majority of patients with CLD ultimately progress to liver cirrhosis and hepatic failure, necessitating liver transplantation due to the lack of effective treatment. Recent investigations have underscored the pivotal role of the gut microbiota-bile acid axis in the progression of hepatic fibrosis via various pathways. The obstruction of bile drainage can induce gut microbiota dysbiosis and disrupt the intestinal mucosal barrier, leading to bacteria translocation. The microbial translocation activates the immune response and promotes liver fibrosis progression. The identification of therapeutic targets for modulating the gut microbiota-bile acid axis represents a promising strategy to ameliorate or perhaps reverse liver fibrosis in CLD. This review focuses on the mechanisms in the gut microbiota-bile acids axis in CLD and highlights potential therapeutic targets, aiming to lay a foundation for innovative treatment approaches.
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Affiliation(s)
- Dayan Sun
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Chuanping Xie
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Yong Zhao
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Junmin Liao
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Shuangshuang Li
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Yanan Zhang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Dingding Wang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Kaiyun Hua
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Yichao Gu
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Jingbin Du
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China
| | - Guoxian Huang
- Department of Pediatric Surgery, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361000, China
| | - Jinshi Huang
- Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nalishi Road, Xicheng District, Beijing, 100045, China.
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Wang Y, Tu J, Wu W, Xu Y, Li Y, Pan X, Liu B, Lu T, Han Q, Zhang H, Jiao L, Zhang Y, Yu XY, Shen Z, Li Y. The orchestration of cell-cycle reentry and ribosome biogenesis network is critical for cardiac repair. Theranostics 2024; 14:3927-3944. [PMID: 38994017 PMCID: PMC11234283 DOI: 10.7150/thno.96460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 06/18/2024] [Indexed: 07/13/2024] Open
Abstract
Rationale: Myocardial infarction (MI) is a severe global clinical condition with widespread prevalence. The adult mammalian heart's limited capacity to generate new cardiomyocytes (CMs) in response to injury remains a primary obstacle in developing effective therapies. Current approaches focus on inducing the proliferation of existing CMs through cell-cycle reentry. However, this method primarily elevates cyclin dependent kinase 6 (CDK6) and DNA content, lacking proper cytokinesis and resulting in the formation of dysfunctional binucleated CMs. Cytokinesis is dependent on ribosome biogenesis (Ribo-bio), a crucial process modulated by nucleolin (Ncl). Our objective was to identify a novel approach that promotes both DNA synthesis and cytokinesis. Methods: Various techniques, including RNA/protein-sequencing analysis, Ribo-Halo, Ribo-disome, flow cytometry, and cardiac-specific tumor-suppressor retinoblastoma-1 (Rb1) knockout mice, were employed to assess the series signaling of proliferation/cell-cycle reentry and Ribo-bio/cytokinesis. Echocardiography, confocal imaging, and histology were utilized to evaluate cardiac function. Results: Analysis revealed significantly elevated levels of Rb1, bur decreased levels of circASXL1 in the hearts of MI mice compared to control mice. Deletion of Rb1 induces solely cell-cycle reentry, while augmenting the Ribo-bio modulator Ncl leads to cytokinesis. Mechanically, bioinformatics and the loss/gain studies uncovered that circASXL1/CDK6/Rb1 regulates cell-cycle reentry. Moreover, Ribo-Halo, Ribo-disome and circRNA pull-down assays demonstrated that circASXL1 promotes cytokinesis through Ncl/Ribo-bio. Importantly, exosomes derived from umbilical cord mesenchymal stem cells (UMSC-Exo) had the ability to enhance cardiac function by facilitating the coordinated signaling of cell-cycle reentry and Ribo-bio/cytokinesis. These effects were attenuated by silencing circASXL1 in UMSC-Exo. Conclusion: The series signaling of circASXL1/CDK6/Rb1/cell-cycle reentry and circASXL1/Ncl/Ribo-bio/cytokinesis plays a crucial role in cardiac repair. UMSC-Exo effectively repairs infarcted myocardium by stimulating CM cell-cycle reentry and cytokinesis in a circASXL1-dependent manner. This study provides innovative therapeutic strategies targeting the circASXL1 signaling network for MI and offering potential avenues for enhanced cardiac repair.
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Affiliation(s)
- Yanli Wang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Junchu Tu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Weiliang Wu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Yan Xu
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P. R. China
| | - Yujie Li
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Xiangbin Pan
- Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, Key Laboratory of Cardiovascular Apparatus Innovation, Beijing 100037, P. R. China
| | - Bin Liu
- Department of Cardiology, the Second Hospital of Jilin University, Changchun, Jilin 130041, P. R. China
| | - Tonggan Lu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Qingfang Han
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Huiling Zhang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Lijuan Jiao
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Yu Zhang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Xi-Yong Yu
- Key Laboratory of Molecular Target & Clinical Pharmacology and the NMPA State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong 511436, P. R. China
| | - Zhenya Shen
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
| | - Yangxin Li
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, P. R. China
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Liu H, Yuan S, Liu G, Li J, Zheng K, Zhang Z, Zheng S, Yin L, Li Y. Satellite Cell-Derived Exosomes: A Novel Approach to Alleviate Skeletal Muscle Atrophy and Fibrosis. Adv Biol (Weinh) 2024; 8:e2300558. [PMID: 38329214 DOI: 10.1002/adbi.202300558] [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: 10/16/2023] [Revised: 01/17/2024] [Indexed: 02/09/2024]
Abstract
Skeletal muscle atrophy coincides with extensive fibrous tissue hyperplasia in muscle-atrophied patients, and fibrous tissue plays a vital role in skeletal muscle function and hinders muscle fiber regeneration. However, effective drugs to manage skeletal muscle atrophy and fibrosis remain elusive. This study isolated and characterized exosomes derived from skeletal muscle satellite cells (MuSC-Exo). The study investigated their effects on denervated skeletal muscle atrophy and fibrosis in Sprague Dawley (SD) rats via intramuscular injection. MuSC-Exo demonstrated the potential to alleviate skeletal muscle atrophy and fibrosis. The underlying mechanism using single-cell RNA sequencing data and functional analysis are analyzed. Mechanistic studies reveal close associations between fibroblasts and myoblasts, with the transforming growth factor β1 (TGF-β1)-Smad3-Pax7 axis governing fibroblast activation in atrophic skeletal muscle. MuSC-Exo intervention inhibited the TGF-β1/Smad3 pathway and improved muscle atrophy and fibrosis. In conclusion, MuSC-Exo-based therapy may represent a novel strategy to alleviate skeletal muscle atrophy and reduce excessive fibrotic tissue by targeting Pax7 through the TGF-β1/Smad3 pathway.
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Affiliation(s)
- Hongwen Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
- Department of Discipline Construction Office, Panzhihua Central Hospital, Panzhihua, Sichuan, 617067, China
| | - Shiguo Yuan
- Department of Orthopaedic, Hainan Traditional Chinese Medicine Hospital, Haikou, Hainan, 570203, China
- School of Chinese Medicine, Hainan Medical University, Haikou, Hainan, 571199, China
| | - Gaofeng Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Junhua Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Kai Zheng
- Department of Orthopaedic, Hainan Traditional Chinese Medicine Hospital, Haikou, Hainan, 570203, China
- School of Chinese Medicine, Hainan Medical University, Haikou, Hainan, 571199, China
| | - Zhiwei Zhang
- Department of Orthopaedic, Hainan Traditional Chinese Medicine Hospital, Haikou, Hainan, 570203, China
- School of Chinese Medicine, Hainan Medical University, Haikou, Hainan, 571199, China
| | - Sheng Zheng
- Department of Traditional Chinese Orthopedics and Traumatology, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, 510630, China
| | - Li Yin
- Department of Discipline Construction Office, Panzhihua Central Hospital, Panzhihua, Sichuan, 617067, China
| | - Yikai Li
- Department of Traditional Chinese Orthopedics and Traumatology, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, 510630, China
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Li X, Ji LJ, Feng KD, Huang H, Liang MR, Cheng SJ, Meng XD. Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome. World J Gastroenterol 2024; 30:527-541. [PMID: 38463022 PMCID: PMC10921143 DOI: 10.3748/wjg.v30.i6.527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/21/2023] [Accepted: 01/09/2024] [Indexed: 02/05/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease. Despite ongoing advances in our understanding of UC, its pathogenesis is yet unelucidated, underscoring the urgent need for novel treatment strategies for patients with UC. Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules, such as proteins, RNAs, DNA, and metabolites. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β (IL-1β) and IL-18, triggering the inflammatory response to a pathogenic agent or injury. Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome, with vital roles in the pathological process of UC. Here, recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC. First, the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized. Finally, an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are highlighted.
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Affiliation(s)
- Xin Li
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou Province, China
| | - Li-Jiang Ji
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, Jiangsu Province, China
| | - Kai-Di Feng
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Hua Huang
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, Jiangsu Province, China
| | - Mei-Rou Liang
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Shi-Jin Cheng
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xiu-Dong Meng
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou Province, China
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Wu R, Hu X, Wang J. Current optimized strategies for stem cell-derived extracellular vesicle/exosomes in cardiac repair. J Mol Cell Cardiol 2023; 184:13-25. [PMID: 37801756 DOI: 10.1016/j.yjmcc.2023.09.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 09/10/2023] [Accepted: 09/20/2023] [Indexed: 10/08/2023]
Abstract
Ischemic heart diseases remain the leading cause of death globally, and stem cell-based therapy has been investigated as a potential approach for cardiac repair. Due to poor survival and engraftment in the cardiac ischemic milieu post transplantation, the predominant therapeutic effects of stem cells act via paracrine actions, by secreting extracellular vesicles (EVs) and/or other factors. Exosomes are nano-sized EVs of endosomal origin, and now viewed as a major contributor in facilitating myocardial repair and regeneration. However, EV/exosome therapy has major obstacles before entering clinical settings, such as limited production yield, unstable biological activity, poor homing efficiency, and low tissue retention. This review aims to provide an overview of the biogenesis and mechanisms of stem cell-derived EV/exosomes in the process of cardiac repair and discuss the current advancements in different optimized strategies to produce high-yield EV/exosomes with higher bioactivity, or engineer them with improved homing efficiency and therapeutic potency. In particular, we outline recent findings toward preclinical and clinical translation of EV/exosome therapy in ischemic heart diseases, and discuss the potential barriers in regard to clinical translation of EV/exosome therapy.
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Affiliation(s)
- Rongrong Wu
- Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310009, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou 310009, PR China
| | - Xinyang Hu
- Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310009, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou 310009, PR China; Research Center for Life Science and Human Health, Binjiang Institute of Zhejiang University, Hangzhou 310053, PR China.
| | - Jian'an Wang
- Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310009, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou 310009, PR China; Research Center for Life Science and Human Health, Binjiang Institute of Zhejiang University, Hangzhou 310053, PR China.
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Li H, Guan J, Chen J, Sun W, Chen H, Wen Y, Chen Q, Xie S, Zhang X, Tao A, Yan J. Necroptosis signaling and NLRP3 inflammasome cross-talking in epithelium facilitate Pseudomonas aeruginosa mediated lung injury. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166613. [PMID: 36470578 DOI: 10.1016/j.bbadis.2022.166613] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 11/09/2022] [Accepted: 11/25/2022] [Indexed: 12/07/2022]
Abstract
Pseudomonas aeruginosa induced acute lung injury is such a serious risk to public health, but the pathological regulation remains unclear. Here, we reported that PA mediated epithelial necroptosis plays an important role in pathological process. Pharmacological and genomic ablation of necroptosis signaling ameliorate PA mediated ALI and pulmonary inflammation. Our results further proved NLRP3 inflammasome to involve in the process. Mechanism investigation revealed the cross-talking between inflammasome activation and necroptosis that MLKL-dependent necroptosis signaling promotes the change of mitochondrial membrane potential for the release of reactive oxygen species (ROS), which is the important trigger for functional inflammasome activation. Furthermore, antioxidants such as Mito-TEMPO was confirmed to significantly restrain inflammasome activation in epithelium, resulting in a reduction in PA induced pulmonary inflammation. Taken together, our findings revealed that necroptosis-triggered NLRP3 inflammasome in epithelium plays a crucial role in PA mediated injury, which could be a potential therapeutic target for pulmonary inflammation.
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Affiliation(s)
- Haoyang Li
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Jieying Guan
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Jiaqian Chen
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Weimin Sun
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Honglv Chen
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Yuhuan Wen
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Qile Chen
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Shiyun Xie
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Xueyan Zhang
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China; School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Ailin Tao
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China
| | - Jie Yan
- The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou 510260, China.
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9
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Wang X, Hu S, Zhu D, Li J, Cheng K, Liu G. Comparison of extruded cell nanovesicles and exosomes in their molecular cargos and regenerative potentials. NANO RESEARCH 2023; 16:7248-7259. [PMID: 37223430 PMCID: PMC9971669 DOI: 10.1007/s12274-023-5374-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/30/2022] [Accepted: 12/03/2022] [Indexed: 05/25/2023]
Abstract
Extracellular vesicles (EVs) generated from mesenchymal stem cells (MSCs) play an essential role in modulating cell-cell communication and tissue regeneration. The clinical translation of EVs is constrained by the poor yield of EVs. Extrusion has recently become an effective technique for producing a large scale of nanovesicles (NVs). In this study, we systematically compared MSC NVs (from extrusion) and EVs (from natural secretion). Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs. Additionally, microRNAs in NVs are related to cardiac repair, fibrosis repression, and angiogenesis. Lastly, intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction. Electronic Supplementary Material Supplementary material (Figs. S1-S4) is available in the online version of this article at 10.1007/s12274-023-5374-3.
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Affiliation(s)
- Xianyun Wang
- Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050000 China
- Scientific Research Data Center, The First Hospital of Hebei Medical University, Shijiazhuang, 050000 China
- Hebei Key Laboratory of Cardiac Injury Repair Mechanism Study, Shijiazhuang, 050000 China
- Hebei International Joint Research Center for Structural Heart Disease, Shijiazhuang, 050000 China
- Department of Molecular Biomedical Science, North Carolina State University, Raleigh, North Carolina 27607 USA
- Department of Biomedical Engineering, University of North Carolina, Chapel Hill and North Carolina State University, Raleigh, North Carolina 27607 USA
| | - Shiqi Hu
- Department of Molecular Biomedical Science, North Carolina State University, Raleigh, North Carolina 27607 USA
- Department of Biomedical Engineering, University of North Carolina, Chapel Hill and North Carolina State University, Raleigh, North Carolina 27607 USA
| | - Dashuai Zhu
- Department of Molecular Biomedical Science, North Carolina State University, Raleigh, North Carolina 27607 USA
- Department of Biomedical Engineering, University of North Carolina, Chapel Hill and North Carolina State University, Raleigh, North Carolina 27607 USA
| | - Junlang Li
- Department of Molecular Biomedical Science, North Carolina State University, Raleigh, North Carolina 27607 USA
- Department of Biomedical Engineering, University of North Carolina, Chapel Hill and North Carolina State University, Raleigh, North Carolina 27607 USA
| | - Ke Cheng
- Department of Molecular Biomedical Science, North Carolina State University, Raleigh, North Carolina 27607 USA
- Department of Biomedical Engineering, University of North Carolina, Chapel Hill and North Carolina State University, Raleigh, North Carolina 27607 USA
| | - Gang Liu
- Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050000 China
- Hebei Key Laboratory of Cardiac Injury Repair Mechanism Study, Shijiazhuang, 050000 China
- Hebei International Joint Research Center for Structural Heart Disease, Shijiazhuang, 050000 China
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10
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Janakiram NB, Motherwell JM, Goldman SM, Dearth CL. Efficacy of non-surgical interventions for promoting improved functional outcomes following acute compartment syndrome: A systematic review. PLoS One 2022; 17:e0274132. [PMID: 36083984 PMCID: PMC9462829 DOI: 10.1371/journal.pone.0274132] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/22/2022] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND Acute compartment syndrome (ACS) is a devastating complication which develops following a traumatic extremity injury that results in increased pressure within osteofascial compartments, thereby leading to ischemia, muscle and nerve necrosis, and creates a life-threatening condition if left untreated. Fasciotomy is the only available standard surgical intervention for ACS. Following fasciotomy the affected extremity is plagued by prolonged impairments in function. As such, an unmet clinical need exists for adjunct, non-surgical therapies which can facilitate accelerated functional recovery following ACS. Thus, the purpose of this systematic review was to examine the state of the literature for non-surgical interventions that aim to improve muscle contractile functional recovery of the affected limb following ACS. METHODS English language manuscripts which evaluated non-surgical interventions for ACS, namely those which evaluated the function of the affected extremity, were identified as per PRISMA protocols via searches within three databases from inception to February 2022. Qualitative narrative data synthesis was performed including: study characteristics, type of interventions, quality, and outcomes. Risk of bias (RoB) was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE) RoB tool and reported level of evidence for each article. RESULTS Upon review of all initially identified reports, 29 studies were found to be eligible and included. 23 distinct non-surgical interventions were found to facilitate improved muscle contractile function following ACS. Out of 29 studies, 15 studies which evaluated chemical and biological interventions, showed large effect sizes for muscle function improvement. CONCLUSIONS This systematic review demonstrated that the majority of identified non-surgical interventions facilitated an improvement in muscle contractile function following pathological conditions of ACS.
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Affiliation(s)
- Naveena B. Janakiram
- DoD-VA Extremity Trauma and Amputation Center of Excellence, Bethesda, MD, United States of America
- Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, United States of America
| | - Jessica M. Motherwell
- DoD-VA Extremity Trauma and Amputation Center of Excellence, Bethesda, MD, United States of America
- Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, United States of America
| | - Stephen M. Goldman
- DoD-VA Extremity Trauma and Amputation Center of Excellence, Bethesda, MD, United States of America
- Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, United States of America
| | - Christopher L. Dearth
- DoD-VA Extremity Trauma and Amputation Center of Excellence, Bethesda, MD, United States of America
- Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, United States of America
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11
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Hu X, Qin H, Yan Y, Wu W, Gong S, Wang L, Jiang R, Zhao Q, Sun Y, Wang Q, Wang S, Zhao H, Liu J, Yuan P. Exosomal circular RNAs: Biogenesis, effect, and application in cardiovascular diseases. Front Cell Dev Biol 2022; 10:948256. [PMID: 36016651 PMCID: PMC9395648 DOI: 10.3389/fcell.2022.948256] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/13/2022] [Indexed: 11/13/2022] Open
Abstract
As natural nanoparticles, exosomes regulate a wide range of biological processes via modulation of its components, including circular RNAs (circRNAs). CircRNAs are a novel class of closed-loop single-stranded RNAs with a wide distribution, and play diverse biological roles. Due to its stability in exosomes, exosomal circRNAs serve as biomarkers, pathogenic regulators and exert therapeutic potentials in some cardiovascular diseases, including atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, heart failure, and peripheral artery disease. In this review, we detailed the current knowledge on the biogenesis and functions of exosomes, circRNAs, and exosomal circRNAs, as well as their involvement in these cardiovascular diseases, providing novel insights into the diagnosis and treatment of these diseases.
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Affiliation(s)
- Xiaoyi Hu
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hongran Qin
- Department of Nuclear Radiation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yi Yan
- Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children’s Medical Center, National Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wenhui Wu
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Sugang Gong
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Lan Wang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Rong Jiang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Qinhua Zhao
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yuanyuan Sun
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Qian Wang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Bismuth Science, University of Shanghai for Science and Technology, Shanghai, China
| | - Shang Wang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hui Zhao
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- Institute of Bismuth Science, University of Shanghai for Science and Technology, Shanghai, China
| | - Jinming Liu
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- *Correspondence: Jinming Liu, ; Ping Yuan,
| | - Ping Yuan
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- *Correspondence: Jinming Liu, ; Ping Yuan,
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12
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Banerjee SK, Chatterjee A, Gupta S, Nagar A. Activation and Regulation of NLRP3 by Sterile and Infectious Insults. Front Immunol 2022; 13:896353. [PMID: 35663964 PMCID: PMC9161712 DOI: 10.3389/fimmu.2022.896353] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022] Open
Abstract
Nod-Like Receptor (NLR) is the largest family of Pathogen Recognition Receptors (PRRs) that patrols the cytosolic environment. NLR engagement drives caspase-1 activation that cleaves pro-IL-1B which then gets secreted. Released IL-1B recruits immune cells to the site of infection/injury. Caspase-1 also cleaves Gasdermin-D (GSDM-D) that forms pores within the plasma membrane driving inflammatory cell death called pyroptosis. NLRP3 is the most extensively studied NLR. The NLRP3 gene is encoded by 9 exons, where exon 1 codes for pyrin domain, exon 3 codes for NACHT domain, and Leucine Rich Repeat (LRR) domain is coded by exon 4-9. Exon 2 codes for a highly disorganized loop that connects the rest of the protein to the pyrin domain and may be involved in NLRP3 regulation. The NLRP3 inflammasome is activated by many structurally divergent agonists of microbial, environmental, and host origin. Activated NLRP3 interacts with an adaptor protein, ASC, that bridges it to pro-Caspase-1 forming a multi-protein complex called inflammasome. Dysregulation of NLRP3 inflammasome activity is a hallmark of pathogenesis in several human diseases, indicating its highly significant clinical relevance. In this review, we summarize the existing knowledge about the mechanism of activation of NLRP3 and its regulation during activation by infectious and sterile triggers.
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Affiliation(s)
- Srijon K. Banerjee
- Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
| | - Ayan Chatterjee
- Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Shamba Gupta
- Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, NY, United States
| | - Abhinit Nagar
- Flow Cytometry, Luminex Corporation, Austin, TX, United States
- *Correspondence: Abhinit Nagar,
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13
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The Mechanisms Underlying the Beneficial Effects of Stem Cell-Derived Exosomes in Repairing Ischemic Tissue Injury. J Cardiovasc Transl Res 2022; 15:524-534. [PMID: 35484464 DOI: 10.1007/s12265-022-10263-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 04/20/2022] [Indexed: 12/12/2022]
Abstract
Ischemic diseases are life-threatening, and the incidence increases as people's lifestyles change. Medications and surgical intervention offer limited benefit, and stem cell therapy has emerged as a potential approach for treating ischemic diseases. The exosomes secreted by stem cells have attracted more attention because they do not trigger the immune response and can be used as drug carriers. The non-coding RNA (ncRNA) carried by exosomes plays a key role in mediating exosome's beneficial effect, which can be further enhanced when combined with nanomaterials to improve its retention time. Here, we review the downstream target molecules and signal pathways of ncRNA and summarize recent advances of some nanomaterials used to encapsulate exosomes and promote ischemic tissue repair. We highlight the imprinting of exosomes from parent cells and discuss how the inflammasome pathway may be targeted for the development of novel therapy for ischemic diseases.
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14
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Wang S, Zhao X, Liu Q, Wang Y, Li S, Xu S. Selenoprotein K protects skeletal muscle from damage and is required for satellite cells-mediated myogenic differentiation. Redox Biol 2022; 50:102255. [PMID: 35144051 PMCID: PMC8844831 DOI: 10.1016/j.redox.2022.102255] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/23/2022] [Accepted: 01/28/2022] [Indexed: 12/11/2022] Open
Abstract
The regeneration of adult skeletal muscle after injury is primarily initiated by satellite cells (SCs), but the regulatory mechanisms of cells committed to myogenic differentiation remain poorly explored. Small molecular selenoprotein K (SelK) plays crucial roles in the modulation of endoplasmic reticulum (ER) stress and against oxidative stress. Here, we first showed that SelK expression is activated in myogenic cells during differentiation both in vivo and in vitro. Meanwhile, loss of SelK delayed skeletal muscle regeneration, inhibited the development of myoblasts into myotubes, and was accompanied by reduced expression of myogenic regulatory factors (MRFs). Moreover, ER stress, intracellular reactive oxygen species (ROS), autophagy and apoptosis under myogenesis induction were more severe in SelK-deficient mice and cells than in the corresponding control groups. Supplementation with specific inhibitors to alleviate excessive ER stress or oxidative stress partly rescued the differentiation potential and formation of myotubes. Notably, we demonstrated that Self-mediated regulation of cellular redox status was primarily derived from its subsequent effects on ER stress. Together, our results suggest that SelK protects skeletal muscle from damage and is a crucial regulator of myogenesis.
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Affiliation(s)
- Shengchen Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Xia Zhao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Qingqing Liu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Yue Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Shu Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
| | - Shiwen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
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15
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Li Z, Chen X, Tao J, Shi A, Zhang J, Yu P. Exosomes Regulate NLRP3 Inflammasome in Diseases. Front Cell Dev Biol 2022; 9:802509. [PMID: 35047512 PMCID: PMC8762245 DOI: 10.3389/fcell.2021.802509] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 12/03/2021] [Indexed: 12/11/2022] Open
Abstract
Emerging evidence has suggested the unique and critical role of exosomes as signal molecules vector in various diseases. Numerous researchers have been trying to identify how these exosomes function in immune progression, as this could promote their use as biomarkers for the disease process and potential promising diagnostic tools. NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3), a tripartite protein, contains three functional domains a central nucleotide-binding and oligomerization domain (NACHT), an N-terminal pyrin domain (PYD), and a leucine-rich repeat domain (LRR). Of note, existing studies have identified exosome as a novel mediator of the NLRP3 inflammasome, which is critical in diseases progression. However, the actual mechanisms and clinical treatment related to exosomes and NLRP3 are still not fully understood. Herein, we presented an up-to-date review of exosomes and NLRP3 in diseases, outlining what is known about the role of exosomes in the activation of NLRP3 inflammasome and also highlighting areas of this topic that warrant further study.
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Affiliation(s)
- Zhangwang Li
- The Second Affiliated Hospital of Nanchang University, The Second Clinical Medical College of Nanchang University, Nanchang, China
| | - Xinyue Chen
- The Second Affiliated Hospital of Nanchang University, The Second Clinical Medical College of Nanchang University, Nanchang, China
| | - Junjie Tao
- The Second Affiliated Hospital of Nanchang University, The Second Clinical Medical College of Nanchang University, Nanchang, China
| | - Ao Shi
- School of Medicine, University of Nicosia, Nicosia, Cyprus.,School of Medicine, St. George University of London, London, United Kingdom
| | - Jing Zhang
- The Second Affiliated Hospital of Nanchang University, The Second Clinical Medical College of Nanchang University, Nanchang, China.,Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Peng Yu
- The Second Affiliated Hospital of Nanchang University, The Second Clinical Medical College of Nanchang University, Nanchang, China.,Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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16
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Shen X, Song S, Chen N, Liao J, Zeng L. Stem cell-derived exosomes: A supernova in cosmetic dermatology. J Cosmet Dermatol 2021; 20:3812-3817. [PMID: 34536054 DOI: 10.1111/jocd.14438] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/23/2021] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Stem cell-derived exosomes are cell-free vesicles secreted by stem cells. Exosomes play a pivotal role in cell-to cell communication due to the functional proteins and genetic information which they carry. In addition, studies on cell migration, tumor invasion, tissue regeneration, myocardial repair after injury, and fracture healing have been widely reported. OBJECTIVES The purpose of this review is to sum up the current state of research on multiple stem cell-derived exosomes in cosmetic dermatology and to discuss the current challenges and future directions. METHODS We searched "skin" and "exosome" from PubMed to find the application of stem cell exosomes in cosmetic dermatology. RESULTS We found that stem cell-derived exosomes have an important place in skin cosmetology such as wound healing, skin aging, and scar formation. CONCLUSION Stem cell derived exosomes supply a potential tool to cosmetic dermatology. The performance of stem cell derived exosomes in regulating skin physiological and pathobiological functions suggests that stem cell derived exosomes have potential in cosmetic dermatology.
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Affiliation(s)
- Xu Shen
- Department of Medical Cosmetology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Shenghua Song
- Department of Medical Cosmetology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Nian Chen
- Department of Medical Cosmetology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Junlin Liao
- Department of Medical Cosmetology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Li Zeng
- Department of Medical Cosmetology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
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