[Effect of angiotensin II on transforming growth factor beta-induced fibroblast proliferation in human skin].

OBJECTIVE: To observe the effect of angiotensin II (Ang II) or/and transforming growth factor beta (TGF-beta) on human skin fibroblast proliferation, and to explore the possible signaling mechanism involved in their actions. METHODS: Cultured human skin fibroblasts were treated with different concentrations of Ang II (1 x 10(-10), 1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) mol/L) , TGF-beta(0.1, 1.0 and 10.0 ng/ml), and 1 x 10(-10) mol/L Ang II + 0.1 ng/ml TGF-beta, respectively. The cell proliferation was determined by 3H-thymidine (3H-TdR) incorporation. The phosphorylation of extracellular signal-regulated kinases (ERK) was detected by Western blot. RESULTS: Ang II at 1 x 10(-9), 1 x 10(-8), 1 x 10(-7) mol/L or TGF-beta at 1.0, 10.0 ng/ml increased 3H-TdR incorporation into cultured skin fibroblasts dose-dependently. Ang II and TGF-beta at lower doses (1 x 10(-10) mol/L and 0.1 ng/ml, respectively) did not affect 3H-TdR incorporation into fibroblasts (P>0.05), whereas co-administration of both Ang II and TGF-beta at these doses significantly increased 3H-TdR incorporation into fibroblasts (P<0.05). Ang II at 1 x 10(-7) mol/L or TGF-beta at 10.0 ng/ml significantly increased ERK phosphorylation of fibroblasts after stimulation (P<0.01). Smaller doses of Ang II (1 x 10(-10) mol/L) or TGF-beta (0.1 ng/ml) did not influence ERK phosphorylation of fibroblasts, whereas co-administration of Ang II and TGF-beta at these doses significantly enhanced ERK phosphorylation (P<0.05). Total protein levels of ERK did not differ at different doses. CONCLUSION: These results indicate that Ang II and TGF-beta synergistically increase skin fibroblast proliferation, which is at least partly via enhancement of ERK activity.