MiR-638靶向Teashirt3调控人血管平滑肌细胞表型转化的研究

Vascular smooth muscle cell (VSMC) phenotypic switch is an important initial step of VSMC proliferation and migration in the development of a number of cardiovascular diseases. However, the molecular mechanisms underlying the SMC phenotypic switch still remains unclear. Based on my previous study, miR-638 was markedly down-regulated in the synthetic VSMC phenotype, whereas expression was markedly increased during VSMC differentiation. Furthermore, we demonstrated that overexpression of miR-638 increased expression of VSMC differentiation marker genes. Moreover, in an attempt to identify targets of miR-638, we utilized TargetScan and identified Teashirt3 as a potential target gene of miR-638. According to our previous results, the purpose of this study is to investigate whether miR-638 plays a role in human VSMC phenotypic switch and the dowmstream regulational mechanism, combined with in vivo study on mouse carotid artery ligation model, in order to discuss the expression and effects of miR-638 and potential target gene on the pathogenesis and progression of neointima formation after arterial ligation.This study will further explore the potential of miR-638 as an attractive therapeutic target for the treatment of proliferative vascular disease, such as atherosclerosis and restenosis.

血管平滑肌细胞（VSMC）表型转化是血管增殖性疾病中VSMC增殖和迁移的关键起始步骤，但是其调控机制尚不明确。申请人前期研究发现，miR-638在合成型人VSMCs中表达降低，在收缩型VSMCs中表达升高；过表达miR-638可上调VSMC分化标志基因的表达，提示miR-638可能参与VSMC表型转化的调控。利用生物信息学进一步发现Teashirt3 可能是 miR-638 调节 VSMC 表型转化的靶基因。本课题拟通过建立人VSMC表型转化模型，深入研究miR-638对人VSMC表型转化过程的影响以及验证miR-638在VSMC表型转化中的靶基因；构建小鼠颈动脉结扎模型，通过转染腺病毒过表达miR-638,阐明miR-638在动脉损伤后新生内膜增殖中的作用;探讨miR-638及其潜在靶基因在人VSMC表型转化中的调控机制，为探索miR-638作为血管增殖性疾病治疗的新靶点提供理论依据。

血管平滑肌细胞（VSMC）表型转化是血管增殖性疾病中VSMC增殖和迁移的关键起始步骤，但是其调控机制尚不明确。申请人前期研究发现，miR-638在合成型人VSMCs中表达降低，在收缩型VSMCs中表达升高；过表达miR-638可上调VSMC分化标志基因的表达，提示miR-638可能参与VSMC表型转化的调控。利用生物信息学进一步发现Teashirt3 可能是 miR-638 调节 VSMC 表型转化的靶基因。本课题拟通过建立人VSMC表型转化模型，深入研究miR-638对人VSMC表型转化过程的影响以及验证miR-638在VSMC表型转化中的靶基因；构建小鼠颈动脉结扎模型，通过转染腺病毒过表达miR-638,阐明miR-638在动脉损伤后新生内膜增殖中的作用;探讨miR-638及其潜在靶基因在人VSMC表型转化中的调控机制，为探索miR-638作为血管增殖性疾病治疗的新靶点提供理论依据。