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Transient receptor potential vanilloid 4 channel deficiency aggravates tubular damage after acute renal ischaemia reperfusion

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Item Type:Article
Title:Transient receptor potential vanilloid 4 channel deficiency aggravates tubular damage after acute renal ischaemia reperfusion
Creators Name:Mannaa, M. and Markó, L. and Balogh, A. and Vigolo, E. and N'diaye, G. and Kaßmann, M. and Michalick, L. and Weichelt, U. and Schmidt-Ott, K.M. and Liedtke, W.B. and Huang, Y. and Müller, D.N. and Kuebler, W.M. and Gollasch, M.
Abstract:Transient receptor potential vanilloid 4 (TRPV4) cation channels are functional in all renal vascular segments and mediate endothelium-dependent vasorelaxation. Moreover, they are expressed in distinct parts of the tubular system and activated by cell swelling. Ischaemia/reperfusion injury (IRI) is characterized by tubular injury and endothelial dysfunction. Therefore, we hypothesised a putative organ protective role of TRPV4 in acute renal IRI. IRI was induced in TRPV4 deficient (Trpv4 KO) and wild-type (WT) control mice by clipping the left renal pedicle after right-sided nephrectomy. Serum creatinine level was higher in Trpv4 KO mice 6 and 24 hours after ischaemia compared to WT mice. Detailed histological analysis revealed that IRI caused aggravated renal tubular damage in Trpv4 KO mice, especially in the renal cortex. Immunohistological and functional assessment confirmed TRPV4 expression in proximal tubular cells. Furthermore, the tubular damage could be attributed to enhanced necrosis rather than apoptosis. Surprisingly, the percentage of infiltrating granulocytes and macrophages were comparable in IRI-damaged kidneys of Trpv4 KO and WT mice. The present results suggest a renoprotective role of TRPV4 during acute renal IRI. Further studies using cell-specific TRPV4 deficient mice are needed to clarify cellular mechanisms of TRPV4 in IRI.
Keywords:Acute Kidney Injury, Animal Disease Models, Apoptosis, Ischemia, Kidney, Kidney Tubules, Knockout Mice, Reperfusion, Reperfusion Injury, TRPV Cation Channels, Animals, Mice
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:4878
Date:20 March 2018
Official Publication:https://doi.org/10.1038/s41598-018-23165-0
PubMed:View item in PubMed

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