NDLI: Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion.

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Erin J. Debruin Michael R. Hughes Christina Sina Alex Lu Jessica Cait Zhiqi Jian Martin Lopez Bernard Lo Thomas Abraham Kelly M. McNagny
Abstract	Despite the widespread use of CD34-family sialomucins (CD34, podocalyxin and endoglycan) as vascular endothelial cell markers, there is remarkably little known of their vascular function. Podocalyxin (gene name Podxl), in particular, has been difficult to study in adult vasculature as germ-line deletion of podocalyxin in mice leads to kidney malformations and perinatal death. We generated mice that conditionally delete podocalyxin in vascular endothelial cells (Podxl(ΔEC) mice) to study the homeostatic role of podocalyxin in adult mouse vessels. Although Podxl(ΔEC) adult mice are viable, their lungs display increased lung volume and changes to the matrix composition. Intriguingly, this was associated with increased basal and inflammation-induced pulmonary vascular permeability. To further investigate the etiology of these defects, we isolated mouse pulmonary endothelial cells. Podxl(ΔEC) endothelial cells display mildly enhanced static adhesion to fibronectin but spread normally when plated on fibronectin-coated transwells. In contrast, Podxl(ΔEC) endothelial cells exhibit a severely impaired ability to spread on laminin and, to a lesser extent, collagen I coated transwells. The data suggest that, in endothelial cells, podocalyxin plays a previously unrecognized role in maintaining vascular integrity, likely through orchestrating interactions with extracellular matrix components and basement membranes, and that this influences downstream epithelial architecture.
e-ISSN	19326203
DOI	10.1371/journal.pone.0108881
Journal	PLoS ONE
Issue Number	10
Volume Number	9
Language	English
Publisher	Public Library of Science (PLoS)
Publisher Date	2014-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Medicine Science
Content Type	Text
Resource Type	Article

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