{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T16:32:00Z","timestamp":1771259520479,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI-EX107-10736SI"],"award-info":[{"award-number":["NHRI-EX107-10736SI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["106-2314-B-182A-141 -MY3"],"award-info":[{"award-number":["106-2314-B-182A-141 -MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8I0941"],"award-info":[{"award-number":["CMRPG8I0941"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8G1342"],"award-info":[{"award-number":["CMRPG8G1342"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNA-29 (miR-29) has been found to reduce liver inflammation and fibrosis following a liver injury. Meanwhile, DNA methyltransferase has been reported to participate in the development of non-alcoholic steatohepatitis (NASH). The aim of this study is to investigate the miR-29a regulation of methyltransferase signaling and epigenetic program in NASH progression. Methods: miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates were subjected to the methionine-choline-deficient (MCD) diet-induced animal model of NASH. Primary hepatic stellate cells were transfected with a miR-29a mimic and antisense inhibitor. We then analyzed gene expressions with qRT-PCR, immunohistochemical stain, Western blot, and luciferase reporter assay. The results demonstrated that increased miR-29a alleviated the MCD diet-induced body weight loss and steatosis and decreased aspartate aminotransferase (AST) levels in mice. Furthermore, hepatic tissue in miR-29aTg mice displayed a weak fibrotic matrix, as shown with Sirius Red staining concomitant with low fibrotic \u03b1-SMA expression within affected tissues compared to the wild-type mice fed the MCD diet. Forced miR-29a expression reduced the MCD diet exaggeration of reactive oxygen species (ROS) production by immunohistochemically staining 8-OHdG. Increased miR-29a signaling also resulted in the downregulation of DNMT3b, TGF-\u03b2, IL-6, heme oxygenase-1 (HO-1), p-SMAD3, PI3K, and L3BII expression within the liver tissue. An in vitro luciferase reporter assay further confirmed that miR-29a mimic transfection reduced DNMT3b expression in primary HSCs. Our data provide new insights that miR-29a improves MCD diet-induced liver inflammation, steatosis and fibrosis, and highlight the potential of miR-29a targeted therapy for treating NASH.<\/jats:p>","DOI":"10.3390\/ijms20061499","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T05:03:12Z","timestamp":1553662992000},"page":"1499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["MicroRNA-29a Disrupts DNMT3b to Ameliorate Diet-Induced Non-Alcoholic Steatohepatitis in Mice"],"prefix":"10.3390","volume":"20","author":[{"given":"Ya-Ling","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsing-Chun","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Nursing, Chang Gung University of Science and Technology, Chiayi 600, Taiwan"},{"name":"Reseach Fellow, Chiayi Chang Gung Memorial Hospital, Chiayi 600, Taiwan"},{"name":"Research Center for the Industry of Human Ecology and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 330, Taiwan"},{"name":"Chronic Diseases and Health Promotion Research Center, CGUST, Chiayi 600, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng-Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Core Laboratory for Phenomics &amp; Diagnostics, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7127-0046","authenticated-orcid":false,"given":"Ying-Hsien","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease: A systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1053\/j.gastro.2010.09.038","article-title":"Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study","volume":"140","author":"Williams","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/hep.25772","article-title":"The Nonalcoholic Steatohepatitis Clinical Research Network. 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