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 (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.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Debruin
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hughes
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Sina
authors.forename: Alex
authors.initials: A
authors.lastname: Lu
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Liu
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cait
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Jian
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Lopez
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lo
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Vancouver, BC, Canada; Penn State College of Medicine, Penn State University, Hershey, Pennsylvania, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Abraham
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D017353:Gene Deletion; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012795:Sialoglycoproteins; C001643:podocalyxin