Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion

Erin J. Debruin, Michael R. Hughes, Christina Sina, Alex Liu, Jessica Cait, Zhiqi Jian, Martin Lopez, Bernard Lo, Thomas Abraham, Kelly M. McNagny

Research output: Contribution to journalArticle

20 Scopus citations

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 (PodxlΔEC mice) to study the homeostatic role of podocalyxin in adult mouse vessels. Although PodxlΔEC 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. PodxlΔEC endothelial cells display mildly enhanced static adhesion to fibronectin but spread normally when plated on fibronectin-coated transwells. In contrast, PodxlΔEC endothelial cells exhibit a severely impaired ability to spread on laminin, 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.

Original languageEnglish (US)
Article numbere108881
JournalPloS one
Volume9
Issue number10
DOIs
StatePublished - Oct 10 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Debruin, E. J., Hughes, M. R., Sina, C., Liu, A., Cait, J., Jian, Z., Lopez, M., Lo, B., Abraham, T., & McNagny, K. M. (2014). Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion. PloS one, 9(10), [e108881]. https://doi.org/10.1371/journal.pone.0108881