Yoon JH, Lee YS, Kim O, Ashktorab H, Smoot DT, Nam SW, Park WS. NKX6.3 protects against gastric mucosal atrophy by downregulating β-amyloid production. World J Gastroenterol 2019; 25(3): 330-345 [PMID: 30686901 DOI: 10.3748/wjg.v25.i3.330]
Corresponding Author of This Article
Won Sang Park, MD, PhD, Doctor, Professor, Department of Pathology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, South Korea. wonsang@catholic.ac.kr
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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Yoon JH, Lee YS, Kim O, Ashktorab H, Smoot DT, Nam SW, Park WS. NKX6.3 protects against gastric mucosal atrophy by downregulating β-amyloid production. World J Gastroenterol 2019; 25(3): 330-345 [PMID: 30686901 DOI: 10.3748/wjg.v25.i3.330]
World J Gastroenterol. Jan 21, 2019; 25(3): 330-345 Published online Jan 21, 2019. doi: 10.3748/wjg.v25.i3.330
NKX6.3 protects against gastric mucosal atrophy by downregulating β-amyloid production
Jung Hwan Yoon, Yeon Soo Lee, Olga Kim, Hassan Ashktorab, Duane T Smoot, Suk Woo Nam, Won Sang Park
Jung Hwan Yoon, Olga Kim, Suk Woo Nam, Won Sang Park, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Jung Hwan Yoon, Suk Woo Nam, Won Sang Park, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Yeon Soo Lee, Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Hassan Ashktorab, Department of Medicine, Howard University, Washington, DC 20060, United States
Duane T Smoot, Department of Medicine, Meharry Medical Center, Nashville, TN 37208, United States
Author contributions: Yoon JH performed the majority of experiments, analyzed and interpreted the data, acquired funding and contributed to manuscript writing; Lee YS and Kim O reviewed and edited the manuscript; Ashktorab H and Smoot DT provided HFE-145 cells; Nam SW reviewed and edited the manuscript and helped in data interpretation; Park WS conceived the project, interpreted the data, acquired funding and wrote the manuscript.
Supported bythe Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, No. 2018R1A2A2A14019713 to Park WS.
Institutional review board statement: The study was approved by the Institutional Review Board of The Catholic University of Korea, College of Medicine (MC16SISI0130).
Conflict-of-interest statement: The authors disclose no potential conflicts of interest.
Data sharing statement: No data are available.
Corresponding author: Won Sang Park, MD, PhD, Doctor, Professor, Department of Pathology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, South Korea. wonsang@catholic.ac.kr
Telephone: +82-2-22587310 Fax: +82-2-5376586
Received: October 18, 2018 Peer-review started: October 18, 2018 First decision: November 29, 2018 Revised: December 21, 2018 Accepted: December 21, 2018 Article in press: December 21, 2018 Published online: January 21, 2019 Processing time: 95 Days and 22.5 Hours
Core Tip
Core tip: In human gastric epithelial cells, NKX6.3 depletion induced production of amyloid β (Aβ) oligomers, and also increased expression of apolipoprotein E (ApoE), Aβ, β-secretase 1 (Bace1), nicastrin, and receptor for advanced glycosylation end product proteins. Moreover, NKX6.3 depletion leads to stably formed of γ-secretase complex and binding to Bace1 protein. In gastric mucosae with atrophy, expression of Aβ oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Additionally, treatment with recombinant Aβ 1-42 produced oligomeric forms of Aβ and significantly decreased cell viability in NKX6.3 depleting cells. These observations provide evidences that NKX6.3 can inhibit gastric mucosal atrophy by regulating Aβ peptide accumulation and inflammatory reaction in gastric epithelial cells.
