c-Cbl泛素化调控JAK2/STAT3途径对早产儿视网膜血管新生的作用研究

早产儿视网膜病变（Retinopathy of Prematurity ROP）的主要病理特征是玻璃体和视网膜内血管新生以及增殖性改变，机制尚不完全清楚。申请人发现，通过生物学分析的方法预测出原癌基因c-Cbl与眼部血管新生有关，但具体机制不明。本课题将研究JAK2/STAT3信号途径与c-Cbl之间的关系以及二者在ROP发病中的作用。首先观察c-Cbl与JAK2对内皮细胞的生长和管腔形成的影响；其次分析c-Cbl与JAK2之间的相互作用、c-Cbl对STAT3转录活性的调节以及c-Cbl对STAT3下游靶基因的影响；最后，我们将构建ROP小鼠模型，通过质粒转染干扰眼内c-Cbl表达后，观察玻璃体、视网膜新生血管的生长并分析眼内相关蛋白的表达。预期研究结果可能进一步丰富人们对ROP发病机制的认识，为发现新的治疗靶点提供理论和实验依据。

The main pathological features of retinopathy of prematurity(ROP) is neovascularization and proliferation of vetrous body and retina, but the mechanism is not known well. Recently, by using the biologic analysis method, we found that oncogene c-Cbl is involved in the development of ocular neovascularization with an unclear mechanism. Focusing on the JAK2/STAT3 signaling pathway, this study is designed to, firstly, observe the effect of c-Cbl and JAK2 on angiogenesis tube formation; secondly clarify the interaction of c-Cbl and JAK2、the regulation of c-Cbl for STAT3 and its downstream target genes. In addition, after endogenous c-Cbl interfered by siRNA in ROP model eyes , neovascularization will be observed and the relative protein will be analyzed. So far, there is no report about this. The novel findings would possibly enrich the knowledge about mechanism of ROP and provide scientific basis for the treatment.