{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T16:03:46Z","timestamp":1769270626895,"version":"3.49.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>Background\/Aims: Recently, microRNAs (miRNAs) have been demonstrated to act as regulators of activation of hepatic stellate cells (HSCs). It is well known that the main profibrogenic inducer transforming growth factor-\u03b21 (TGF-\u03b21) contributes to HSC activation, which is a key event in liver fibrosis. Increasing studies show that miR-9-5p is down-regulated in liver fibrosis and restoration of miR-9-5p limits HSC activation. However, the role of miR-9-5p in TGF-\u03b21-induced HSC activation is still not clear. Methods: miR-9-5p expression was quantified using real-time PCR in chronic hepatitis B (CHB) patients and TGF-\u03b21-treated LX-2 cells. In CHB patients, histological activity index (HAI) and fibrosis stages were assessed using the Ishak scoring system. Effects of miR-9-5p on liver fibrosis in vivo and in vitro were analyzed. Luciferase activity assays were performed to examine the binding of miR-9-5p to the 3\u2032-untranslated region of type I TGF-\u03b2 receptor (TGFBR1) as well as TGFBR2. Results: Compared with healthy controls, miR-9-5p was reduced in CHB patients. There was a lower miR-9-5p expression in CHB patients with higher fibrosis scores or HAI scores. miR-9-5p was down-regulated by TGF-\u03b21 in a dose-dependent manner. TGF-\u03b21-induced HSC activation including cell proliferation, \u03b1-SMA and collagen expression was blocked down by miR-9-5p. Notably, miR-9-5p ameliorates carbon tetrachloride-induced liver fibrosis. As determined by luciferase activity assays, TGFBR1 and TGFBR2 were targets of miR-9-5p. Further studies demonstrated that miR-9-5p inhibited TGF-\u03b21\/Smads pathway via TGFBR1 and TGFBR2. Interestingly, promoter methylation was responsible for miR-9-5p down-regulation in liver fibrosis. The relationship between miR-9-5p expression and methylation was confirmed in CHB patients and TGF-\u03b21-treated cells. Conclusion: Our results demonstrate that miR-9-5p could inhibit TGF-\u03b21-induced HSC activation through TGFBR1 and TGFBR2. Loss of miR-9-5p is associated with its methylation status in liver fibrosis.<\/jats:p>","DOI":"10.1159\/000484303","type":"journal-article","created":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T21:02:23Z","timestamp":1509051743000},"page":"2242-2252","source":"Crossref","is-referenced-by-count":37,"title":["Epigenetically-Regulated MicroRNA-9-5p Suppresses the Activation of Hepatic Stellate Cells via TGFBR1 and TGFBR2"],"prefix":"10.1159","volume":"43","author":[{"given":"Fujun","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"BiCheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"XuFei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guojun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peihong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjian","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2017,10,27]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/484303","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/484303","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/484303","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:09:57Z","timestamp":1745428197000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000484303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,12,18]]}},"URL":"https:\/\/doi.org\/10.1159\/000484303","archive":["Portico"],"relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}