Department of Pathology, Geisel School of Medicine at Dartmouth, Hanover, NH 03756, USA.
Dev Cell. 2012 Dec 11;23(6):1203-18. doi: 10.1016/j.devcel.2012.11.003.
Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.
窗孔和气孔隔膜是内皮细胞亚细胞结构，其功能未知，形成于涉及血管通透性的细胞器上：窗孔、细胞间通道和小窝。PV1 蛋白是体外形成隔膜所必需的。在这里，我们报告说，在小鼠中删除编码 Plvap 基因的 PV1 基因导致隔膜缺失和存活率降低。隔膜的缺失并不影响窗孔和细胞间通道的形成，但破坏了有窗孔毛细血管的屏障功能，导致大量血浆蛋白渗漏。这种破坏导致动物因严重的非炎症性蛋白丢失性肠病而早期死亡。内皮细胞中而非造血细胞中删除 PV1 可重现整体 PV1 缺失的表型，而内皮细胞中重建 PV1 可挽救该表型。总之，这些数据为隔膜在维持血液成分方面对有窗孔毛细血管的关键作用提供了遗传证据。
