Podocalyxin is required for maintaining blood-brain barrier function during acute inflammation

Proceedings of the National Academy of Sciences of the United States of America
Jessica CaitK M McNagny

Abstract

Podocalyxin (Podxl) is broadly expressed on the luminal face of most blood vessels in adult vertebrates, yet its function on these cells is poorly defined. In the present study, we identified specific functions for Podxl in maintaining endothelial barrier function. Using electrical cell substrate impedance sensing and live imaging, we found that, in the absence of Podxl, human umbilical vein endothelial cells fail to form an efficient barrier when plated on several extracellular matrix substrates. In addition, these monolayers lack adherens junctions and focal adhesions and display a disorganized cortical actin cytoskeleton. Thus, Podxl has a key role in promoting the appropriate endothelial morphogenesis required to form functional barriers. This conclusion is further supported by analyses of mutant mice in which we conditionally deleted a floxed allele of Podxl in vascular endothelial cells (vECs) using Tie2Cre mice (PodxlΔTie2Cre). Although we did not detect substantially altered permeability in naïve mice, systemic priming with lipopolysaccharide (LPS) selectively disrupted the blood-brain barrier (BBB) in PodxlΔTie2Cre mice. To study the potential consequence of this BBB breach, we used a selective agonist (TFLLR-NH2) of t...Continue Reading

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Citations

Jul 25, 2020·Scientific Reports·Hannah W SongEric V Shusta
Jul 1, 2020·Frontiers in Pharmacology·Maria VähätupaHannele Uusitalo-Järvinen
Nov 28, 2020·Journal for Immunotherapy of Cancer·Diana Canals HernaezKelly M McNagny
Mar 26, 2021·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Ayçağ YorgancıA Seval Ozgu-Erdinc
Jul 3, 2021·Cancers·Ngoc Le TranGuiying Nie
Oct 2, 2021·Cellular & Molecular Immunology·Ian Galea
Dec 17, 2021·Frontiers in Medicine·Barbara J BallermannBörje Haraldsson

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