MicroRNA Regulation Of Cell Survival In Angiogenesis & Vessel Maturation

描述（由申请人提供）：称为“血管生成”的血管的异常生长导致从黄斑变性、视网膜病到炎症和癌症的几种人类疾病的病理学。最近，基因组中编码的称为microRNA的小RNA已经涉及包括血管生成在内的多种生理过程的调节。我们最近分析了内皮细胞活化过程中的microRNA，并确定microRNA-132是病理性新生血管形成过程中p120 RasGAP的关键调节因子。在这个提议中，我将在指导阶段使用体外和体内血管生成模型来描述miR-132/p120 RasGAP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，我将分析一种不同的microRNA的贡献，它在血管细胞中起着细胞存活的负调节作用。这些研究将阐明不同的microRNA程序如何在发育和疾病过程中控制血管系统中促血管生成和抗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.