Ang II induces proliferation and collagen synthesis in rat pancreatic stellate cells

Objective:To investigate the effects of Ang Ⅱ on cellular proliferation and activation of cultured rat pancreatic stellate cells(PSCs).Methods: Growth arrest was induced in the 4~(th)-7~(th) passage rat PSCs by culturing with serum-free DMEM for 48 h,then the PSCs were incubated for 24 h or 48 h with serum-free culture medium containing different concentrations of Ang Ⅱ(0,1,10,and 100 nmol/L) in the presence or absence of ZD7155 and PD123319,the specific antagonists of Ang Ⅱ type 1 and 2 receptors(AT1 and AT2).The DNA synthesis rate was investigated by using [~(3)H]thymidine incorporation,collagen synthesis rate by [~(3)H]proline incorporation,α-smooth muscle actin(α-SMA) expression by Western blot analysis,and procollagen α1(Ⅰ) mRNA expression by Northern blot analysis.Results: Treatment of cells with Ang Ⅱ for 24 h resulted in a dose-dependent increase in DNA synthesis,with statistically significant increase at 10 and 100 nmol/L(both P0.05 vs normal control).Treatment for 48 h with Ang Ⅱ at concentrations of 1,10,and 100 nmol/L dose-dependently induced collagen synthesis and procollagen α1(Ⅰ) mRNA expression(both P0.05 vs normal control).The above effects of Ang Ⅱ(100 nmol/L) were inhibited by ZD7155(P0.01 vs Ang Ⅱ alone) but not by PD123319(P0.05 vs Ang Ⅱ alone).No significant increase in the expression of α-SMA protein was observed in response to stimulation with increasing concentrations of Ang Ⅱ.Conclusion: The present study indicates that Ang Ⅱ,mediated by AT1 receptor,can dose-dependently induce the proliferation and collagen production in rat PSCs,thus participating in the pancreatic fibrogenesis.