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.

中文翻译：

---

Atg7 的内皮耗竭引发星形胶质细胞与血脑屏障处微血管的分离

微血管基底膜（BM）在星形胶质细胞与内皮细胞的相互作用中发挥着关键作用，以维持血脑屏障（BBB）稳态；然而，BBB 中内皮细胞衍生的 BM 成分的重要性和精确调节仍不完全清楚。在这里，我们报告内皮细胞中Atg7的条件性敲除（Atg7-ECKO）导致大脑中星形胶质细胞与微血管的分离。我们的结果揭示了 Atg7-ECKO 小鼠星形胶质细胞末足与微血管的脱离和 BBB 渗漏。此外，我们发现内皮 Atg7 的缺失会下调纤连蛋白（BBB 的主要 BM 成分）的表达，导致星形胶质细胞沿脑微血管的覆盖显着减少。我们发现Atg7通过调节PKA活性来触发内皮纤连蛋白的表达，从而影响cAMP反应元件结合蛋白的磷酸化。这些结果表明，Atg7 调节的内皮纤连蛋白的产生是星形胶质细胞粘附到微血管壁以维持 BBB 稳态所必需的。因此，内皮 Atg7 在星形胶质细胞-内皮相互作用中发挥重要作用，以维持 BBB 完整性。