Involvement of 90-kuD ribosomal S6 kinase in collagen type I expression in rat hepatic fibrosis

Miao Fang Yang, Jun Xie, Xiao Yi Gu, Xiao Hua Zhang, Andrew K. Davey, Shuang Jie Zhang, Ji Ping Wang, Ren Min Zhu

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3 Citations (Scopus)

Abstract

Aim: To investigate the relationship between 90-kuD ribosomal S6 kinase (p90RSK) and collagen type? expression during the development of hepatic fibrosis in vivo and in vitro. Methods: Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type? were determined by co-immunofluoresence and confocal microscopy. Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell (HSC) line. The expression of collagen type? in HSC-T6 cells was assessed by Western blotting and real-time polymerase chain reaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, then collagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated with or without platelet-derived growth factor (PDGF)-BB at a final concentration of 20 μg/L and the cell growth was determined by MTS conversion. Results: In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significant positive correlation with collagen type I levels. In HSC-T6 cells transfected with RNAi targeted to p90RSK, the expression of collagen type? was down-regulated (61.8% in mRNA, P < 0.01, 89.1% in protein, P < 0.01). However, collagen type I promoter activity was not increased with over-expression of p90RSK and not decreased with low expression either, compared with controls in the same cell line (P = 0.076). Furthermore, p90RSK siRNA exerted the inhibition of HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation. Conclusion: p90RSK is over-expressed in activated HSCs and involved in regulating the abnormal expression of collagen type? through initiating the proliferation of HSCs.

Original languageEnglish
Pages (from-to)2109-2115
Number of pages7
JournalWorld Journal of Gastroenterology
Volume15
Issue number17
DOIs
Publication statusPublished - 7 May 2009
Externally publishedYes

Keywords

  • 90-kuD ribosomal S6 kinase
  • Collagen type I
  • Hepatic fibrosis
  • Hepatic stellate cell
  • RNAi

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