{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:51:17Z","timestamp":1791093077303,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1157,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"crossref","award":["R01AA014891"],"award-info":[{"award-number":["R01AA014891"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Institutional funds from Carolinas Medical Center"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Hepatic stellate cell (HSC) activation is a pivotal event in initiation and progression of hepatic fibrosis and a major contributor to collagen deposition driven by transforming growth factor beta (TGF-\u03b2). MicroRNAs (miRs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver disease. We investigated differentially expressed miRs in quiescent and activated HSCs to identify novel regulators of profibrotic TGF-\u03b2 signaling. miR microarray analysis was performed on quiescent and activated rat HSCs. Members of the miR-17-92 cluster (19a, 19b, 92a) were significantly down-regulated in activated HSCs. Because miR 19b showed the highest fold-change of the cluster members, activated HSCs were transfected with miR 19b mimic or negative control and TGF-\u03b2 signaling and HSC activation assessed. miR 19b expression was determined in fibrotic rat and human liver specimens. miR 19b mimic negatively regulated TGF-\u03b2 signaling components demonstrated by decreased TGF-\u03b2 receptor II (TGF-\u03b2RII) and SMAD3 expression. Computational prediction of miR 19b binding to the 3\u2032 untranslated region of TGF-\u03b2RII was validated by luciferase reporter assay. Inhibition of TGF-\u03b2 signaling by miR 19b was confirmed by decreased expression of type I collagen and by blocking TGF-\u03b2-induced expression of \u03b11(I) and \u03b12(I) procollagen mRNAs. miR 19b blunted the activated HSC phenotype by morphological assessment and decreased smooth muscle \u03b1-actin expression. Additionally, miR 19b expression was markedly diminished in fibrotic rat liver compared with normal liver; similarly, miR 19b expression was markedly down-regulated in fibrotic compared with normal human livers.\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                      miR 19b is a novel regulator of TGF-\u03b2 signaling in HSCs, suggesting a potential therapeutic approach for hepatic fibrosis. 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