Zhuang Shi-Fang, Liu Dong-Xin, Wang Hui-Jie, Zhang Shu-Hong, Wei Jia-Yi, Fang Wen-Gang, Zhang Ke, Cao Liu, Zhao Wei-Dong, Chen Yu-Hua
Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang 110122, China.
Int J Mol Sci. 2017 May 3;18(5):968. doi: 10.3390/ijms18050968.
The formation of brain vasculature is an essential step during central nervous system development. The molecular mechanism underlying brain angiogenesis remains incompletely understood. The role of Atg7, an autophagy-related protein, in brain angiogenesis was investigated in this study. We found that the microvessel density in mice brains with endothelial-specific knockout of Atg7 (Atg7 EKO) was significantly decreased compared to wild-type control. Consistently, in vitro angiogenesis assays showed that Atg7 knockdown impaired angiogenesis in brain microvascular endothelial cells. Further results indicated that knockdown of Atg7 reduced interleukin-6 (IL-6) expression in brain microvascular endothelial cells, which is mediated by NF-κB-dependent transcriptional control. Interestingly, exogenous IL-6 restored the impaired angiogenesis and reduced cell motility caused by Atg7 knockdown. These results demonstrated that Atg7 has proangiogenic activity in brain angiogenesis which is mediated by IL-6 production in a NF-κB-dependent manner.
脑脉管系统的形成是中枢神经系统发育过程中的一个重要步骤。脑 angiogenesis 潜在的分子机制仍未完全了解。本研究调查了自噬相关蛋白 Atg7 在脑 angiogenesis 中的作用。我们发现，与野生型对照相比，内皮细胞特异性敲除 Atg7（Atg7 EKO）的小鼠脑中微血管密度显著降低。一致地，体外 angiogenesis 试验表明，Atg7 敲低损害了脑微血管内皮细胞中的 angiogenesis。进一步的结果表明，Atg7 敲低降低了脑微血管内皮细胞中白细胞介素-6（IL-6）的表达，这是由 NF-κB 依赖性转录控制介导的。有趣的是，外源性 IL-6 恢复了由 Atg7 敲低引起的受损 angiogenesis 并降低了细胞运动性。这些结果表明，Atg7 在脑 angiogenesis 中具有促血管生成活性，这是以 NF-κB 依赖性方式通过 IL-6 产生介导的。
