OBJECTIVE Urocortins(UCNs)and transforming growth factor-β(TGF-β)have been demonstrated to participate in various cardiovascular diseases,many of which involve VSMCs proliferation.And cytosolic phospholipase A2(c PLA2)-mediated arachidonic acid(AA)release is an important cause of vascular smooth muscle cells(VSMCs)proliferation.The work was to investigate the regulation of VSMCs proliferation by UCN/TGF-βand whether c PLA2 was a link between their signaling pathways.METHODS VSMC proliferation was measured by MTT assay and immunofluorescence microscopy.Using cell flow cytometry,the changes in the cell cycle phases were investigated.si RNA was used to knockdown Smad2 and smad3 genes.Lentiviral Vector Particle was performed to over express c PLA2 gene.RESULTS Both UCN and TGF-βinhibited VSMCs proliferation and an additive effect was observed when the cells were treated with UCN plus TGF-β.TGF-βincreased the percentage of cells in G1-phase while UCN increased the cell percentage in G2-phase with a concomitant decrease in S-phase.Neither knockdown of smad2 nor smad3 reversed the role of TGF-β.Furthermore,c PLA2expression was increased by TGF-βbut decreased by UCN and UCN attenuated TGF-β-induced c PLA2 expression.In primary VSMCs,TGF-βinduced c PLA2 phosphorylation,and this effect was also attenuated by UCN.Similar to UCN,the c PLA2 inhibitor,pyrrophenone(PYR),also played a role in enhancing TGF-β-mediated mitoinhibition.Inversely,over-expression of c PLA2 eliminated the effect of UCN on the mitoinhibition.CONCLUSION The pretreatment with UCN counteracted TGF-β-mediated c PLA2 expression and activation,thereby contributing to TGF-β-mediated mitoinhibition of VSMCs. OBJECTIVE Urocortins (UCNs) and transforming growth factor-β (TGF-β) have been introduced to various cardiovascular diseases, many of which involve VSMCs proliferation. And cytosolic phospholipase A2 (c PLA2) -mediated arachidonic acid (AA) release is an important cause of vascular smooth muscle cells (VSMCs) proliferation. The work was to investigate the regulation of proliferation of VSMCs by UCN / TGF-β and whether c PLA2 was a link between their signaling pathways. METHODS VSMC proliferation was measured by MTT assay and immunofluorescence microscopy. Using cell flow cytometry, the changes in the cell cycle phases were investigated. si RNA was used to knockdown Smad2 and smad3 genes.Lentiviral Vector Particle was performed to over express c PLA2 gene .RESULTS Both UCN and TGF-β inhibited VSMCs proliferation and an additive effect was observed when the cells were treated with UCN plus TGF-β.TGF-βincreased the percentage of cells in G1-phase while UCN increased the cell percentage in G 2-phase with a concomitant decrease in S-phase. Neither knockdown of smad2 nor smad3 reversed the role of TGF-β.Furthermore, c PLA2 expression was increased by TGF-β but decreased by UCN and UCN attenuated TGF-β-induced c PLA2 expression .In primary VSMCs, TGF-βinduced c PLA2 phosphorylation, and this effect was also attenuated by UCN.Similar to UCN, the c PLA2 inhibitor, pyrrophenone (PYR), also played a role in enhancing TGF-β-mediated mitoinhibition.Inversely, over-expression of c PLA2 eliminated the effect of UCN on the mitoinhibition. CONCLUSION The pretreatment with UCN counteracted TGF-β-mediated c PLA2 expression and activation, contributing to TGF-β-mediated mitoinhibition of VSMCs.