Department of Developmental Cell Biology, School of Life Sciences, China Medical University, Shenyang, China.
Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
Anat Rec (Hoboken). 2019 Dec;302(12):2255-2260. doi: 10.1002/ar.24223. Epub 2019 Jul 12.
Cerebral angiogenesis is a key event during brain development and recovery from brain injury. We previously demonstrated that Atg7 knockout impaired angiogenesis in the mouse brain. However, the role of Atg7 in angiogenesis is not completely understood. In this study, we used human brain microvascular endothelial cells (HBMECs) to investigate the mechanism of Atg7-regulated cerebral angiogenesis. We found that Atg7 depletion specifically diminished the expression of the β3 and γ2 chains of laminin-5, a major component of the extracellular matrix. In contrast, autophagy inhibitors did not affect laminin-5 expression, suggesting that Atg7-regulated laminin-5 expression is autophagy-independent. We also found that Atg7-regulated laminin-5 expression occurred at the transcriptional level through NF-κB signaling. Exogenous laminin-5 or the NF-κB agonist betulinic acid effectively rescued tube formation by Atg7-deficient HBMECs. Taken together, our study identified a novel mechanism by which Atg7 regulates laminin-5 expression via NF-κB to modulate tube formation by brain endothelial cells during cerebral angiogenesis. Anat Rec, 302:2255-2260, 2019. © 2019 American Association for Anatomy.
脑血管生成是脑发育和脑损伤恢复过程中的一个关键事件。我们之前的研究表明，Atg7 敲除会损害小鼠大脑中的血管生成。然而，Atg7 在血管生成中的作用尚不完全清楚。在这项研究中，我们使用人脑微血管内皮细胞（HBMEC）来研究 Atg7 调节脑血管生成的机制。我们发现 Atg7 缺失特异性地减少了层粘连蛋白-5 的β3 和γ2 链的表达，层粘连蛋白-5 是细胞外基质的主要成分之一。相比之下，自噬抑制剂不会影响层粘连蛋白-5 的表达，这表明 Atg7 调节的层粘连蛋白-5 表达是独立于自噬的。我们还发现，Atg7 通过 NF-κB 信号调节层粘连蛋白-5 的表达发生在转录水平上。外源性层粘连蛋白-5 或 NF-κB 激动剂桦木酸有效地挽救了 Atg7 缺陷的 HBMEC 形成管状结构的能力。总之，我们的研究确定了一种新的机制，即 Atg7 通过 NF-κB 调节层粘连蛋白-5 的表达，从而调节脑内皮细胞在脑血管生成过程中的管状结构形成。解剖学记录，302:2255-2260, 2019。©2019 美国解剖学会。
