β-
Arrestins are multifunctional adaptor
proteins. Recently, some new roles of β-
arrestins in regulating intracellular signaling networks have been discovered, which regulate cell growth, proliferation, and apoptosis. Though, the role of β-
arrestins expression in the pathology of hepatic
fibrosis remains unclear. In this study, the possible relationship between the expression of β-
arrestins 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 β-arrestin1, β-arrestin2, and α-smooth muscle actin (α-SMA) 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 β-arrestin2 in the hepatic tissues, but not β-arrestin1. Further, as hepatic
fibrosis worsens, β-arrestin2-expressing activated HSCs accounts for an increasingly larger percentage of all activated HSCs. And the expression of β-arrestin2 had a significant positive correlation with the expression of α-SMA, an activated HSCs marker. In vitro studies, the dynamic expression of β-arrestin1 and β-arrestin2 in
platelet derived growth factor-BB (
PDGF-BB) stimulated HSCs was assessed by Western blotting. The expression of β-arrestin2 was remarkably increased in
PDGF-BB stimulated HSCs. Furthermore, the
small interfering RNA (
siRNA) technique was used to explore the effect of β-
arrestins on the proliferation of HSCs and the activation of ERK1/2. Transfection of
siRNA targeting β-arrestin2
mRNA (siβ-arrestin2) into HSCs led to a 68% and 70% reduction of β-arrestin2
mRNA and
protein expression, respectively. siβ-arrestin2 abolished the effect of
PDGF-BB on the proliferation of HSCs. In addition, siβ-arrestin2 exerted the inhibition of the activation of ERK1/2 in HSCs. The present study provided strong evidence for the participation of the β-arrestin2 in the pathogenesis of hepatic
fibrosis. The β-arrestin2 depletion diminishes HSCs ERK1/2 signaling and proliferation stimulated by
PDGF-BB. Selective targeting of β-arrestin2 inhibitors to HSCs might present as a novel strategy for the treatment of hepatic
fibrosis.