Vangl2, a planar cell polarity molecule, is implicated in irreversible and reversible kidney glomerular injury

Papakrivopoulou, Eugenia and Vasilopoulou, Elisavet and Lindenmeyer, Maja T and Pacheco, Sabrina and Brzóska, Hortensja ? and Price, Karen L and Kolatsi-Joannou, Maria and White, Kathryn E and Henderson, Deborah J and Dean, Charlotte H and Cohen, Clemens D and Salama, Alan D and Woolf, Adrian S and Long, David A (2018) Vangl2, a planar cell polarity molecule, is implicated in irreversible and reversible kidney glomerular injury. Journal of Pathology, . ISSN 0022-3417. (doi:https://doi.org/10.1002/path.5158) (Full text available)

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https://doi.org/10.1002/path.5158

Abstract

Planar cell polarity (PCP) pathways control the orientation and alignment of epithelial cells within tissues. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for normal differentiation of kidney glomeruli and tubules. Vangl2 has also been implicated in modifying the course of acquired glomerular disease and here we further explored how Vangl2 impacts on glomerular pathobiology in this context. Targeted genetic deletion of Vangl2 in mouse glomerular epithelial podocytes enhanced the severity of not only irreversible accelerated nephrotoxic nephritis but also lipopolysaccharide-induced reversible glomerular damage. In each proteinuric model, genetic deletion of Vangl2 in podocytes was associated with an increased ratio of active-MMP9 to inactive MMP9, an enzyme involved in tissue remodelling. Additionally, by interrogating microarray data from two cohorts of renal patients, we report increased VANGL2 transcript levels in glomeruli of individuals with focal segmental glomerulosclerosis, suggesting that the molecule may also be involved in certain human glomerular diseases. These observations support the conclusion that Vangl2 modulates glomerular injury, at least in part by acting as a brake on MMP9, a potentially harmful endogenous enzyme.

Item Type: Article
Uncontrolled keywords: glomerulus, kidney disease, matrix metalloproteinase, planar cell polarity, podocyte
Subjects: Q Science > QR Microbiology
R Medicine
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: E. Vasilopoulou
Date Deposited: 27 Oct 2018 15:36 UTC
Last Modified: 30 Oct 2018 11:28 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/69815 (The current URI for this page, for reference purposes)
Vasilopoulou, Elisavet: https://orcid.org/0000-0002-1940-0333
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