Endothelial depletion of Atg7 triggers astrocyte-microvascular disassociation at blood-brain barrier

Liu et al. identify that the endothelium-derived fibronectin production regulated by Atg7 is required for the astrocytes attachment to microvascular wall. Endothelial Atg7 deficiency suppresses fibronectin via PKA/CREB signaling. This study uncovers the autophagy-independent function of endothelial Atg7 in the maintenance of the BBB integrity. Microvascular basement membrane (BM) plays a pivotal role in the interactions of astrocyte with endothelium to maintain the blood-brain barrier (BBB) homeostasis; however, the significance and precise regulation of the endothelial cell-derived BM component in the BBB remain incompletely understood. Here, we report that conditional knockout of Atg7 in endothelial cells (Atg7-ECKO) leads to astrocyte-microvascular disassociation in the brain. Our results reveal astrocytic endfeet detachment from microvessels and BBB leakage in Atg7-ECKO mice. Furthermore, we find that the absence of endothelial Atg7 downregulates the expression of fibronectin, a major BM component of the BBB, causing significantly reduced coverage of astrocytes along cerebral microvessels. We reveal Atg7 triggers the expression of endothelial fibronectin via regulating PKA activity to affect the phosphorylation of cAMP-responsive element-binding protein. These results suggest that Atg7-regulated endothelial fibronectin production is required for astrocytes adhesion to microvascular wall for maintaining the BBB homeostasis. Thus, endothelial Atg7 plays an essential role in astrocyte-endothelium interactions to maintain the BBB integrity.

Automated summary

Liu et al. have discovered that Atg7, regulated by endothelial cells, is necessary for the attachment of astrocytes to the microvascular wall. Deficiency of endothelial Atg7 suppresses fibronectin through PKA/CREB signaling. This study has revealed the autophagy-independent function of endothelial Atg7 in maintaining the integrity of the blood-brain barrier (BBB).