Atg7 Silencing Inhibits Laminin-5 Expression to Suppress Tube Formation by Brain Endothelial Cells.

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.