Podocalyxin (Podxl) has an essential role in the development and function of the kidney glomerular filtration barrier. It is also expressed by vascular endothelia but perinatal lethality of podxl(-/-) mice has precluded understanding of its function in adult vascular endothelial cells (ECs). In this work, we show that conditional knockout mice with deletion of Podxl restricted to the vascular endothelium grow normally but most die spontaneously around three months of age. Histological analysis showed a nonspecific inflammatory infiltrate within the vessel wall frequently associated with degenerative changes, and involving vessels of different caliber in one or more organs. Podxl-deficient lung EC cultures exhibit increased permeability to dextran and macrophage transmigration. After thrombin stimulation, ECs lacking Podxl showed delayed recovery of VE-cadherin cell contacts, persistence of F-actin stress fibers, and sustained phosphorylation of the ERM complex and activation of RhoA, suggesting a failure in endothelial barrier stabilization. The results suggest that Podxl has an essential role in the regulation of endothelial permeability by influencing the mechanisms involved in the restoration of endothelial barrier integrity after injury.

中文翻译：

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有条件消融内皮细胞中podocalyxin（Podxl）的小鼠中内皮屏障完整性的丧失。

Podocalyxin（Podxl）在肾小球滤过屏障的发育和功能中起着至关重要的作用。它也由血管内皮表达，但podxl（-/-）小鼠的围生期致死性使人们无法理解其在成年血管内皮细胞（EC）中的功能。在这项工作中，我们表明删除限制于血管内皮细胞的Podxl的条件性基因敲除小鼠正常生长，但大多数会在三个月大时自发死亡。组织学分析显示血管壁内的非特异性炎性浸润经常与退行性改变有关，并累及一个或多个器官中不同口径的血管。缺乏Podxl的肺EC培养物对葡聚糖和巨噬细胞转运的通透性增加。凝血酶刺激后 缺乏Podxl的EC表现出VE-钙粘蛋白细胞接触的恢复延迟，F-肌动蛋白应激纤维的持续存在，ERM复合物的持续磷酸化和RhoA的激活，提示内皮屏障稳定作用失败。结果表明，Podxl通过影响损伤后恢复内皮屏障完整性的机制，在调节内皮渗透性中起着至关重要的作用。