{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T02:46:00Z","timestamp":1776134760465,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T00:00:00Z","timestamp":1363219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b2\u2010Arrestins are multifunctional adaptor proteins. Recently, some new roles of \u03b2\u2010arrestins in regulating intracellular signaling networks have been discovered, which regulate cell growth, proliferation, and apoptosis. Though, the role of \u03b2\u2010arrestins expression in the pathology of hepatic fibrosis remains unclear. In this study, the possible relationship between the expression of \u03b2\u2010arrestins with the experimental hepatic fibrosis and the proliferation of hepatic stellate cells (HSCs) were investigated. Porcine serum induced liver fibrosis was established in this study. At five time points, the dynamic expression of \u03b2\u2010arrestin1, \u03b2\u2010arrestin2, and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) in rat liver tissues, was measured by immunohistochemical staining, double immunofluorescent staining, and Western blotting. This study showed that aggravation of hepatic fibrosis with gradually increasing expression of \u03b2\u2010arrestin2 in the hepatic tissues, but not \u03b2\u2010arrestin1. Further, as hepatic fibrosis worsens, \u03b2\u2010arrestin2\u2010expressing activated HSCs accounts for an increasingly larger percentage of all activated HSCs. And the expression of \u03b2\u2010arrestin2 had a significant positive correlation with the expression of \u03b1\u2010SMA, an activated HSCs marker. In vitro studies, the dynamic expression of \u03b2\u2010arrestin1 and \u03b2\u2010arrestin2 in platelet derived growth factor\u2010BB (PDGF\u2010BB) stimulated HSCs was assessed by Western blotting. The expression of \u03b2\u2010arrestin2 was remarkably increased in PDGF\u2010BB stimulated HSCs. Furthermore, the small interfering RNA (siRNA) technique was used to explore the effect of \u03b2\u2010arrestins on the proliferation of HSCs and the activation of ERK1\/2. Transfection of siRNA targeting \u03b2\u2010arrestin2 mRNA (si\u03b2\u2010arrestin2) into HSCs led to a 68% and 70% reduction of \u03b2\u2010arrestin2 mRNA and protein expression, respectively. si\u03b2\u2010arrestin2 abolished the effect of PDGF\u2010BB on the proliferation of HSCs. In addition, si\u03b2\u2010arrestin2 exerted the inhibition of the activation of ERK1\/2 in HSCs. The present study provided strong evidence for the participation of the \u03b2\u2010arrestin2 in the pathogenesis of hepatic fibrosis. The \u03b2\u2010arrestin2 depletion diminishes HSCs ERK1\/2 signaling and proliferation stimulated by PDGF\u2010BB. Selective targeting of \u03b2\u2010arrestin2 inhibitors to HSCs might present as a novel strategy for the treatment of hepatic fibrosis. J. Cell. Biochem. 114: 1153\u20131162, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24458","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T01:33:23Z","timestamp":1354152803000},"page":"1153-1162","source":"Crossref","is-referenced-by-count":20,"title":["Depletion of \u03b2\u2010arrestin2 in hepatic stellate cells reduces cell proliferation via ERK 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