{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:42:14Z","timestamp":1784126534797,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":132,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773979"],"award-info":[{"award-number":["81773979"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373518"],"award-info":[{"award-number":["81373518"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p><jats:italic>Glycyrrhetinic acid<\/jats:italic> (GA), a hydrolysate of <jats:italic>glycyrrhizic acid<\/jats:italic> from licorice root extract, has been used to treat liver fibrotic diseases. However, the molecular mechanism involved in the antifibrotic effects of GA remains unclear. The involvement of miR\u2010663a and its roles in TGF\u2010<jats:italic>\u03b2<\/jats:italic>\u20101\u2010induced hepatic stellate cell (HSC) activation remains unclear. In this study, we investigated the roles of miR\u2010663a in the activation of HSCs and the antifibrosis mechanism of GA. MiR\u2010663a expression was downregulated in TGF\u2010<jats:italic>\u03b2<\/jats:italic>\u2010treated HSCs. The overexpression of miR\u2010663a inhibited HSC proliferation. TGF\u2010<jats:italic>\u03b2<\/jats:italic>\u20101was confirmed as a direct target gene of miR\u2010663a. MiR\u2010663a alleviated HSC activation, concomitant with decreased expression of <jats:italic>\u03b1<\/jats:italic>\u2010smooth muscle actin (<jats:italic>\u03b1<\/jats:italic>\u2010SMA), human <jats:italic>\u03b1<\/jats:italic>2 (I) collagen (COL1A2), TGF\u2010<jats:italic>\u03b2<\/jats:italic>1, TGF\u2010<jats:italic>\u03b2<\/jats:italic>RI, Smad4, p\u2010Smad2, and p\u2010Smad3. GA upregulated miR\u2010663a expression and inhibited the TGF\u2010<jats:italic>\u03b2<\/jats:italic>\/Smad pathway in HSCs. Further studies showed that miR\u2010663a inhibitor treatment reversed GA\u2010mediated downregulation of TGF\u2010<jats:italic>\u03b2<\/jats:italic>1, TGF\u2010<jats:italic>\u03b2<\/jats:italic>RI, Smad4, p\u2010Smad2, p\u2010Smad3, <jats:italic>\u03b1<\/jats:italic>\u2010SMA, and CoL1A2 in TGF\u2010<jats:italic>\u03b2<\/jats:italic>1\u2010treated HSCs. These results show that miR\u2010663a suppresses HSC proliferation and activation and the TGF\u2010<jats:italic>\u03b2<\/jats:italic>\/Smad signaling pathway, highlighting that miR\u2010663a can be utilized as a therapeutic target for hepatic fibrosis. GA inhibits, at least in part, HSC proliferation and activation via targeting the miR\u2010663a\/TGF\u2010<jats:italic>\u03b2<\/jats:italic>\/Smad signaling pathway.<\/jats:p>","DOI":"10.1155\/2020\/3156267","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T23:30:39Z","timestamp":1589326239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["<i>Glycyrrhetinic Acid<\/i>\u2010Induced MiR\u2010663a Alleviates Hepatic Stellate Cell Activation by Attenuating the TGF\u2010<i>\u03b2<\/i>\/Smad Signaling Pathway"],"prefix":"10.1155","volume":"2020","author":[{"given":"Xin-Xin","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Na","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben-Sheng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Wei","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-6424","authenticated-orcid":false,"given":"Shi-Bing","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-2138","authenticated-orcid":false,"given":"Xiu-Li","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5867-1478","authenticated-orcid":false,"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci24282"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7629724"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(14)60121-5"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci88881"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1246-y"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1615\/critreveukaryotgeneexpr.2013007490"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02871"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.09.009"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1257"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.299"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.02.022"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3193"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.06.003"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-013-1895-0"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2018.1"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-4653-y"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.4432"},{"key":"e_1_2_9_18_2","first-page":"2819","article-title":"MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation","volume":"12","author":"Liu Z. 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