肺动脉血管重构是肺动脉高压(PH)发病中的重要病理过程，其发生机制涉及肺动脉血管平滑肌细胞(PASMCs)的异常增殖和抗凋亡表型转换，但其具体机制仍需进一步阐明。申请者在前期研究中，对低氧性肺动脉高压患者血液标本进行microRNA差异表达筛选发现miR-520c表达明显增高。进一步研究证实miR-520c靶向调控LATS2/YAP通路参与肺动脉血管平滑肌细胞增殖的表型转换。本课题拟在此基础上，在肺动脉高压细胞和动物模型中深入研究miR-520c介导肺动脉血管重构中的作用方式及调控机理，阐明转录因子E2F1调控miR-520c转录的分子机制，并通过干预PH动物评价抑制miR-520c对逆转PH血管重构的作用，在临床病例标本中分析miR-520与低氧性肺动脉高压预后的相关性。上述研究将对阐明低氧性肺动脉高压肺血管重构的分子机制具有重要意义，可能为肺动脉高压的提供新的药物作用靶。

Pulmonary vascular remodeling is a key process during the development of pulmonary hypertension (PH), the underlying mechanism of which is closely associated with the gene expression and gene transcription regulation involved in the pulmonary vascular smooth muscle cell (PASMCs) pro-proliferation and anti-apoptosis phenotype switch. MicroRNA, a noncoding RNA molecule, has been demonstrated to be able to regulate the cellular function through modulation of target genes. On the basis of our microRNA chip data and bioinformatics analysis, we identified miR-520c as one of the differential expression gene and investigate the functional role of miR-520c both in vivo and vitro established PH models. By using the miR-520c mimics and inhibitors transfection as well as the luciferase assay, we intend to demonstrate that miR-520c promotes the PASMCs pro-proliferative phenotype by regulating the Hippo/YAP signaling via targeting LATS2. The underlying molecular mechanism through which miR-520c regulates the PASMCs disease phenotype transition is explored by using the LATS2 overexpression and RNA interference. The upstream mechanism of the miR-520 transcription was also investigated by using ChIP assay. The transcription factor E2F1 was involved in the regulation of hypoxia induce miR-520c/LATS2 signal pathway. Finally, we examined the effect of miR-520c inhibition on the vascular remodeling in PH rat models. Together, our research project may provide evidence that E2F1/miR-520c/LATS2 axis serve as a potential therapeutic targets for the treatment of PH.