Article ; Online: Vangl2, a planar cell polarity molecule, is implicated in irreversible and reversible kidney glomerular injury.
2018 Volume 246, Issue 4, Page(s) 485–496
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 the normal differentiation of kidney glomeruli and tubules. Vangl2 has also ... ...
| 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 the 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. In addition, by interrogating microarray data from two cohorts of renal patients, we report increased VANGL2 transcript levels in the 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. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. |
|---|---|
| MeSH term(s) | Adult ; Animals ; Case-Control Studies ; Cell Polarity ; Cells, Cultured ; Disease Models, Animal ; Enzyme Activation ; Female ; Glomerulosclerosis, Focal Segmental/genetics ; Glomerulosclerosis, Focal Segmental/metabolism ; Glomerulosclerosis, Focal Segmental/pathology ; Glomerulosclerosis, Focal Segmental/physiopathology ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Kidney Glomerulus/physiopathology ; Male ; Matrix Metalloproteinase 9/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Nephrosis, Lipoid/genetics ; Nephrosis, Lipoid/metabolism ; Nephrosis, Lipoid/pathology ; Nephrosis, Lipoid/physiopathology ; Nerve Tissue Proteins/deficiency ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Podocytes/metabolism ; Podocytes/pathology ; Signal Transduction ; Young Adult |
| Chemical Substances | Intracellular Signaling Peptides and Proteins ; Ltap protein, mouse ; Membrane Proteins ; Nerve Tissue Proteins ; VANGL2 protein, human ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Mmp9 protein, mouse (EC 3.4.24.35) |
| Language | English |
| Publishing date | 2018-08-17 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 3119-7 |
| ISSN | 1096-9896 ; 0022-3417 |
| ISSN (online) | 1096-9896 |
| ISSN | 0022-3417 |
| DOI | 10.1002/path.5158 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Ud II Zs.12: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.