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

19 Citations (Scopus)

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

Fingerprint

Cell adhesion
Endothelial cells
Capillary Permeability
cell adhesion
blood vessels
Cell Adhesion
endothelial cells
permeability
Endothelial Cells
lungs
Lung
mice
fibronectins
Fibronectins
Blood Vessels
Sialomucins
laminin
basement membrane
Laminin
extracellular matrix

All Science Journal Classification (ASJC) codes

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

Cite this

Debruin, E. J., Hughes, M. R., Sina, C., Liu, A., Cait, J., Jian, Z., ... 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
Debruin, Erin J. ; Hughes, Michael R. ; Sina, Christina ; Liu, Alex ; Cait, Jessica ; Jian, Zhiqi ; Lopez, Martin ; Lo, Bernard ; Abraham, Thomas ; McNagny, Kelly M. / Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion. In: PloS one. 2014 ; Vol. 9, No. 10.
@article{9eae682ce23742c3bf10b2d630d86923,
title = "Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion",
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.",
author = "Debruin, {Erin J.} and Hughes, {Michael R.} and Christina Sina and Alex Liu and Jessica Cait and Zhiqi Jian and Martin Lopez and Bernard Lo and Thomas Abraham and McNagny, {Kelly M.}",
year = "2014",
month = "10",
day = "10",
doi = "10.1371/journal.pone.0108881",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

Debruin, EJ, Hughes, MR, Sina, C, Liu, A, Cait, J, Jian, Z, Lopez, M, Lo, B, Abraham, T & McNagny, KM 2014, 'Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion', PloS one, vol. 9, no. 10, e108881. https://doi.org/10.1371/journal.pone.0108881

Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion. / Debruin, Erin J.; Hughes, Michael R.; Sina, Christina; Liu, Alex; Cait, Jessica; Jian, Zhiqi; Lopez, Martin; Lo, Bernard; Abraham, Thomas; McNagny, Kelly M.

In: PloS one, Vol. 9, No. 10, e108881, 10.10.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion

AU - Debruin, Erin J.

AU - Hughes, Michael R.

AU - Sina, Christina

AU - Liu, Alex

AU - Cait, Jessica

AU - Jian, Zhiqi

AU - Lopez, Martin

AU - Lo, Bernard

AU - Abraham, Thomas

AU - McNagny, Kelly M.

PY - 2014/10/10

Y1 - 2014/10/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907855773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907855773&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0108881

DO - 10.1371/journal.pone.0108881

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e108881

ER -