MicroRNA Regulation Of Cell Survival In Angiogenesis & Vessel Maturation

描述(申请人提供)：血管的异常生长被称为“血管生成”，导致了几种人类疾病的病理，从黄斑变性、视网膜病变到炎症和癌症。最近，基因组中编码的小RNA称为microRNAs，参与了包括血管生成在内的多种生理过程的调节。我们最近对内皮细胞激活过程中的microRNA进行了分析，并发现microRNA-132是病理性新生血管中p120RasGAP的关键调节因子。在这项提案中，我将使用体外和体内指导阶段的血管生成模型来表征miR-132/p120RasGAP在血管系统应激反应期间细胞存活中的作用。使用这些模型，在独立阶段，我将分析不同的microRNA在血管细胞中作为细胞生存负调节因子的作用。这些研究将阐明不同的microRNA程序如何在发育和疾病期间控制血管系统中促血管生成状态和反血管生成状态之间的平衡。

DESCRIPTION (provided by applicant): Aberrant growth of blood vessels termed 'angiogenesis' contributes to the pathology of several human diseases ranging from macular degeneration, retinopathy to inflammation and cancer. Recently small RNAs encoded in the genome termed microRNAs have been implicated in the regulation of diverse physiological processes including angiogenesis. We recently profiled microRNAs during activation of endothelial cells and identified microRNA-132 as a critical regulator of p120RasGAP during pathological neovascularization. In this proposal, I will characterize the role of miR-132/p120RasGAP in cell survival during stress responses in the vasculature using in vitro and in vivo angiogenesis models during the mentored phase. Using these models, in the independent phase, I will analyze the contribution of a different microRNA that functions as a negative regulator of cell survival in vascular cells. These studies will elucidate how distinct microRNA programs govern the balance between the pro and anti-angiogenic states in the vasculature during development and disease.