MicroRNA Regulation Of Cell Survival In Angiogenesis & Vessel Maturation

项目摘要/摘要 被称为“血管生成”的血管的异常生长导致了几种人类疾病的发生 疾病范围从黄斑变性、视网膜病变到炎症和癌症。最近的小RNA 编码在基因组中的microRNAs与多种生理调节有关 包括血管生成在内的各种过程。我们最近分析了内皮细胞激活过程中的microRNA和 发现microRNA-132在病理性新生血管形成过程中是p120RasGAP的关键调节因子。在这 建议，我将表征miR-132/p120RasGAP在应激反应中细胞存活中的作用。 指导阶段使用体外和体内血管生成模型的血管系统。使用这些模型，在 在独立阶段，我将分析作为负性作用的不同microRNA的贡献 维管细胞中细胞存活的调节因子。这些研究将阐明不同的microRNA程序如何管理 血管系统在发育和疾病过程中促血管生成状态和反血管生成状态之间的平衡。

PROJECT SUMMARY/ABSTRACT 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.