Studies On The Effect Of Phentypic Conversion Of Myocardin And STAT3 On Smooth Muscle Cell Proliferation And Diierentiation

The phenotype conversion of vascular smooth muscle cell(VSMC)is a common pathological process in a variety of cardiovascular diseases.It has been shown that STAT3 plays an important role in the proliferation and migration of VSMCs,whereas,Myocardin is critical for the regulation of VSMC differentiation.What would happen if they both exist simultaneously in VSMC and the mechanism are unclear.Therefore,this study focused on the effects of STAT3 and Myocardin co-overexpression and their physical interaction on phenotype conversion.Firstly,the impact of STAT3 activation on HA-VSMCs proliferation and differentiation was determined by luciferase assay,RT-PCR and Western Blot.The results showed that STAT3 activation by VEGF promoted the expression of proliferation marker genes but inhibited differentiation marker genes.On the contrary,with similar methods,Myocardin was found to upregulate differentiation marker genes.Co-everexpression of STAT3 and Myocardin reversed the upregulation of differentiation marker genes.Furthermore,STAT3 and Myocardin were shown by co-IP to physically interact,indicating that STAT3 binds Myocardin thereby inhibit thefunction of Myocardin.Next,to explore the relationship between Myocardin,STAT3 and VEGF,RT-PCR,ELISA and other methods were applied and the results showed that both Myocardin and STAT3 enhanced the expression of VEGF gene.On one hand,VEGF was previously known to activate STAT3,thus,VEGF-STAT3-VEGF form a positive feedback.On the other hand,herein VEGF was found to stimulate the phosphorylation of ERK1/2 which in turn promoted the phosphorylation of Myocardin and thereby inhibited the function of Myocardin.Therefore,VEGF-ERK1/2-Myocardin-VEGF form a negative feedback regulating the phenotype switch of VSMC.Taken togather,STAT3 interacts with Myocardin to regulate the phenotype switch of VSMC.Meanwhile,Myocardin,STAT3 and VEGF form different feedback loops to control the conversion of phenotype.Findings in this study would provide a novel instruction for the therapy of phenotype-switch related cardiovascular diseases.