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Atg7 Regulates Brain Angiogenesis via NF-κB-Dependent IL-6 Production

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 tha...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454881/
https://www.ncbi.nlm.nih.gov/pubmed/28467355
http://dx.doi.org/10.3390/ijms18050968
Descripción
Sumario: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.