Jab1-P53-HIF-1α复合物对VEGF分泌的调节在低氧诱导的视网膜新生血管中的作用

低氧条件下HIF-1α介导的VEGF分泌是视网膜病理性新生血管（RNV）发生的重要原因，但其具体调控机制仍未明确。文献报道Jab1绑定HIF-1α，促进其转录生成VEGF；Jab1绑定P53，促进其出核降解；P53可诱导HIF-1α降解。我们预实验结果发现低氧诱导的视网膜血管内皮细胞（RMECs）中Jab1能与P53和HIF-1α形成三元复合物，并调节RMECs增殖、迁移、内皮管腔形成和VEGF分泌。本研究拟首先在低氧诱导的RMECs中证明Jab1、P53和HIF-1α可形成三元复合物；接着分析干预RMECs中Jab1的表达，对于三元复合物的形成及RMECs增殖、迁移、炎症因子分泌、内皮管腔形成的影响；最后在氧诱导的视网膜病变（OIR）动物模型中干预Jab1表达，阐明对三元复合物形成、VEGF分泌及RNV生成的影响。该研究有望为RNV相关性眼病的防治提供立论依据和新的分子靶点。

VEGF secretion, which mediated by HIF-1α, is an important cause of pathological retinal neovascularization (RNV) under hypoxia condition. However, its specific mechanism is still unclear. It is reported that JAB1 promotes VEGF secretion by binding with HIF-1α. Besides, Jab1 integrates with P53 to promote its degradation. Furthermore, HIF-1α degradation is induced by P53. Our preliminary results showed that in retinal microvascular endothelial cells (RMECs), Jab1 could form ternary complex with P53 and HIF-1α to reduce VEGF secretion and inhibit proliferation, migration of RMECs. In this study, we firstly explored whether Jab1, P53 and HIF-1α could form a ternary complex in hypoxia-induced RMECs. Then we analyzed the formation of ternary complex, the changes of corresponding inflammatory cytokines and angiogenesis of RMECs after Jab1 expression was being suppressed. Finally, the effects of the ternary complex in VEGF secretion and RNV in oxygen-induced retinopathy (OIR) mice were clarified. This study is expected to provide a new molecular target for the prevention and treatment of RNV associated with ophthalmopathy.