Intracellular Signaling Mechanism of the Proliferation and Collagen Synthesis of Cardiac Myofibroblasts Induced by UrotensinⅡ

OBJECTIVE To investigate the effects of urotensin Ⅱ(UⅡ) on the proliferation and collagen synthesis of cardiac myofibroblasts (CFs) of new-born SD rats. METHODS CFs isolated from new-born SD rats were cultured as cell model in vitro. The level of TGF-β1 in CFs supernatant was detected by ELISA assay, and the proliferation and collagen synthesis of CFs treated with UⅡ, SB-611812 and KT5720 were respectively observed by CKK-8 assay and Western blot. RESULTS After CFs treated by 10^-10, 10^-9, 10^-8 mol·L^-1 UⅡ, the level of TGF-β1 in CFs supernatant and the OD values were significantly higher than that in control group(P<0.05), but the indices in the 10^-7 mol·L^-1 UⅡ group were not significantly different from those of control group. The level of TGF-β1 and the OD values in 1 mol·L^-1 SB-611812+10^-8 mol·L^-1 UⅡgroup or 1 mol·L^-1 KT5720+10^-8?mol·L^-1 UⅡ group increased significantly compared with control group(P<0.05), but decreased compared with the 10^-8?mol·L^-1 UⅡ group (P<0.05). The expression of col-Ⅰand col-Ⅲ in 1 mol·L^-1 SB-611812+10^-8 mol·L^-1 UⅡ group and 1 mol·L^-1 KT5720+10^-8 mol·L^-1 UⅡ group decreased significantly compared with the 10^-8 mol·L^-1 UⅡ group. CONCLUSION UⅡcan stimulate the proliferation of CFs by up-regulating the level of TGF-β1 and induce expression of col-Ⅰand col-Ⅲ, the process maybe involve the cAMP-PKA pathway.