Ang II induces proliferation and collagen synthesis in rat pancreatic stellate cells
- Author:
Lin LU
1
Author Information
1. Department of Gastroenterology
- Publication Type:Journal Article
- From:
Academic Journal of Second Military Medical University
2006;27(3):272-275
- CountryChina
- Language:Chinese
-
Abstract:
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 4th-7th 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 [3H]thymidine incorporation, collagen synthesis rate by [3H]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 P<0.05 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 P<0.05 vs normal control). The above effects of Ang II (100 nmol/L) were inhibited by ZD7155 (P<0.01 vs Ang II alone) but not by PD123319 (P>0.05 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.
