MicroRNA Regulation Of Cell Survival In Angiogenesis & Vessel Maturation

项目摘要/摘要 血管的异常生长被称为“血管生成”，导致几种人类肿瘤的病理学改变。 从黄斑变性、视网膜病到炎症和癌症。最近小RNA 在基因组中编码的称为microRNA的基因与多种生理调节有关。 包括血管生成。我们最近分析了内皮细胞活化过程中的microRNA， 鉴定microRNA-132作为病理性新生血管形成过程中p120 RasGAP的关键调节因子。在这 根据这项提议，我将描述miR-132/p120 RasGAP在应激反应中细胞存活中的作用。 在指导阶段期间使用体外和体内血管生成模型对血管系统进行评估。使用这些模型，在 在独立阶段，我将分析一种不同的microRNA的贡献，它的功能是阴性的。 血管细胞中细胞存活的调节因子。这些研究将阐明不同的microRNA程序如何控制 在发育和疾病期间，血管系统中促血管生成和抗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.