Potassium channels: the 'master switch' of renal fibrosis?

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Paolo Menè, Nicola Pirozzi

Abstract

Progressive renal fibrosis resulting from proliferation of interstitial fibroblasts is a hallmark of chronic kidney failure, whatever the origin. The intermediate/small-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) promotes mitogenesis in several cell types by altering the membrane potential, thus enabling extracellular Ca(2+) entry. Grgic et al. evaluated the role of K(Ca)3.1 in renal fibroblast proliferation, testing whether deficiency or pharmacological blockade of K(Ca)3.1 suppressed development of renal fibrosis. Mitogens stimulated K(Ca)3.1 in murine renal fibroblasts via a MEK-dependent mechanism, while selective blockade of K(Ca)3.1 inhibited fibroblast proliferation by promoting G0/G1 arrest. In a classical model of renal fibrosis, mouse unilateral ureteral obstruction (UUO), robust up-regulation of K(Ca)3.1 was detectable in affected kidneys. K(Ca)3.1 KO mice showed reduced expression of fibrotic marker expression, less chronic tubulointerstitial damage, collagen deposition and alpha-smooth muscle+ cells after UUO, with better preservation of functional renal parenchyma. The selective K(Ca)3.1 blocker TRAM-34 similarly attenuated progression of UUO-induced renal fibrosis in wild-type mice and rats. Thus, Grgic ...Continue Reading

References

Feb 7, 2001·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·C R Burrow
Sep 20, 2002·Journal of the American Society of Nephrology : JASN·Junwei YangYouhua Liu
Jan 17, 2003·American Journal of Physiology. Renal Physiology·Junwei Yang, Youhua Liu
Apr 10, 2004·Current Opinion in Nephrology and Hypertension·Masayuki Iwano, Eric G Neilson
Sep 7, 2004·The Journal of Biological Chemistry·Ted BegenisichJames E Melvin
Aug 26, 2006·Nature Clinical Practice. Nephrology·Eric G Neilson
Oct 13, 2006·Journal of the American Society of Nephrology : JASN·Frank Strutz, Michael Zeisberg
Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lina HuPeter A Calabresi
Sep 25, 2007·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Peter BoorJürgen Floege
Dec 14, 2007·Journal of the American Society of Nephrology : JASN·Jürgen FloegeCharles E Alpers
Mar 28, 2008·Expert Review of Molecular Diagnostics·Chuan-Chu ChouNicholas J Murgolo
Aug 9, 2008·The Journal of Clinical Investigation·Kazuyoshi ToyamaHiroto Miura
Aug 30, 2008·Kidney International·Seth L Alper
Nov 7, 2008·Journal of the American Society of Nephrology : JASN·Elisabeth M ZeisbergRaghu Kalluri
Jan 20, 2009·Cardiovascular & Hematological Agents in Medicinal Chemistry·D L Tharp, D K Bowles
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Carla ZojaGiuseppe Remuzzi
Jun 27, 2009·Science·Thaddeus S Stappenbeck, Hiroyuki Miyoshi

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