UNC5B参与年轻血浆改善血管内皮细胞衰老机制探究

血管内皮细胞（VEC）衰老是血管衰老及增龄性疾病发生与发展的重要环节。研究证实年轻血液改善机体多重增龄性改变，血液环境是调控VEC功能及衰老的重要影响因素，但年轻血浆调控VEC衰老作用及机制尚不清楚。我们前期结果显示年轻血浆干预能改善VEC衰老表型，转录组测序分析发现UNC5B在VEC衰老过程中表达上调，但能被年轻血浆干预下调；在年轻VEC上过表达UNC5B加速细胞衰老。因此，我们推测UNC5B参与调控VEC衰老过程。本课题，我们拟通过基因过表达及敲低技术，从离体、在体水平验证UNC5B调控VEC衰老的作用；进一步利用Co-IP、荧光素酶技术、结合通路抑制剂探究UNC5B经由经典衰老信号（P53-P21通路）调控VEC衰老的可能性；同时应用转录组测序技术寻找UNC5B调控下游新靶点及信号通路。为防治VEC衰老，减少增龄性血管疾病，寻找血液中“致青春因子”提供新思路。

Vascular endothelial cell (VEC) senescence is an important links in the occurrence and development of vascular aging and aging-associated diseases. Studies have confirmed that young blood intervention could ameliorate aging phenotype in multiple ways. The blood environment is an important factor in regulating VEC function and senescence. However, the mechanism of young plasma on VEC senescence remain unclear..Our previous results showed that young plasma intervention could improve the VEC senescence phenotype. We used transcriptome sequencing revealed that UNC5B exert pivotal role in the VEC aging processing. Further, we demonstrated that young VEC senescence was accelerated under over-expression of UNC5B..Therefore, we speculate that UNC5B participates in the regulation of VEC senescence process and involved in young plasma intervention..In this study, we intend to verify the role of UNC5B in modulating VEC senescence by gene editing in vitro and in vivo. Further, transcriptome analysis was applied to explore the downstream targets and pathway regulated by UNC5B. Co-IP technology combined with pathway inhibitors was performed to verify the possibility of UNC5B in regulating VEC senescence via classic aging signals (P52-P21 pathway)..This study aimed to explore “young shift genes” to prevent VEC senescence and reduce aging-associated vascular disease.