Abstract:

Objective   To investigate urotensin (UⅡ) and its antagonist urantide(UR) on the synthesis of collagenⅠand Ⅲ in cultured rat pulmonary arterial smooth muscle cells (PASMCs). Methods   Rat pulmonary arterial smooth muscle fragments were isolated and cultured in vitro with explant culture technique, then the harvested cells were used. The effect of UⅡ(1×10-10-1×10-7mol/L) and urantide on the proliferation of PASMCs were measured by BrdU incorporation test. The protein and gene expressions of collagenⅠ and collagen Ⅲ in cultured PASMCs induced by UⅡand Urantide were evaluated by Western blotting and Realtime PCR, respectively. Results   ①UⅡ(1×10-9-1×10-7 mol/L) promoted the proliferation of PASMCs in a dosedependent manner, with maximal effect at a concentration of 1×10-7 mol/L (P<0.05，P<0.001, P<0.001); it also caused a dosedependent increase in collagenⅠand Ⅲ synthesis, with maximal effect at a concentration of 1×10-7 mol/L (P<0.01, P<0.001), while 1×10-10 mol/L UⅡ showed no obvious effect on PASMCs proliferation and the synthesis of collagenⅠand Ⅲ(P>0.05). ②Urantide inhibited UⅡinduced PASMCs proliferation and collagen synthesis (P<0.01). Conclusion   UⅡ binds with UⅡ receptor UT and then activates various signaling pathways, finally, leads to the proliferation of PASMCs and promotes synthesis of collagenⅠand Ⅲ. While, Urantide can competitively bind with UT to inhibit the effects of UⅡon PASMCs.

Key words: UrotensinⅡ； Pulmonary arterial smooth muscle cells； Collagen synthesis； Urantide;  Pulmonary hypertension; Rats，Wistar