Depletion of β-arrestin2 in hepatic stellate cells reduces cell proliferation via ERK pathway

Wu Yi Sun, Yang Song, Shan Shan Hu, Qingtong Wang, Hua Xun Wu, Jing Yu Chen, Wei Wei

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1153-1162
Number of pages10
JournalJournal of Cellular Biochemistry
Volume114
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

Fingerprint

Hepatic Stellate Cells
MAP Kinase Signaling System
Cell proliferation
Cell Proliferation
Arrestins
Fibrosis
Liver
Small Interfering RNA
Messenger RNA
Western Blotting
Chemical activation
Tissue
Staining and Labeling
Cell growth
Pathology
Liver Cirrhosis
Transfection
Muscle
Rats
Actins

Keywords

  • β-arrestin
  • hepatic stellate cell
  • liver fibrosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sun, W. Y., Song, Y., Hu, S. S., Wang, Q., Wu, H. X., Chen, J. Y., & Wei, W. (2013). Depletion of β-arrestin2 in hepatic stellate cells reduces cell proliferation via ERK pathway. Journal of Cellular Biochemistry, 114(5), 1153-1162. https://doi.org/10.1002/jcb.24458

Depletion of β-arrestin2 in hepatic stellate cells reduces cell proliferation via ERK pathway. / Sun, Wu Yi; Song, Yang; Hu, Shan Shan; Wang, Qingtong; Wu, Hua Xun; Chen, Jing Yu; Wei, Wei.

In: Journal of Cellular Biochemistry, Vol. 114, No. 5, 01.05.2013, p. 1153-1162.

Research output: Contribution to journalArticle

Sun, Wu Yi ; Song, Yang ; Hu, Shan Shan ; Wang, Qingtong ; Wu, Hua Xun ; Chen, Jing Yu ; Wei, Wei. / Depletion of β-arrestin2 in hepatic stellate cells reduces cell proliferation via ERK pathway. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 5. pp. 1153-1162.
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