Disruption of guanylyl cyclase-G protects against acute renal injury

Journal of the American Society of Nephrology : JASN
Heng LinRuey-Bing Yang

Abstract

The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G(-/-) mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G(-/-) mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-kappaB were lower in GC-G(-/-) mice compared with wi...Continue Reading

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Citations

Dec 17, 2009·Molecular and Cellular Biochemistry·Sukanya KaranWolfgang Baehr
Oct 16, 2009·Human Reproduction·Ruey-Bing YangYen-Hua Huang
Dec 2, 2009·Transplantation·Irmgard MühlbergerRainer Oberbauer
Apr 3, 2010·Journal of the American Society of Nephrology : JASN·Hsiao-Fen LiRuey-Bing Yang
Nov 20, 2012·Journal of the American Society of Nephrology : JASN·Yi-Fan LanHeng Lin
Sep 15, 2011·Cellular Signalling·Lincoln R Potter
Jan 4, 2015·The EMBO Journal·Michaela Kuhn
Oct 1, 2017·The EMBO Journal·Ying-Chi ChaoRuey-Bing Yang
Jul 15, 2016·American Journal of Physiology. Renal Physiology·Kunyu ShenGlenda C Gobe
Feb 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Beibei WangBin Zhang
Apr 1, 2016·Physiological Reviews·Michaela Kuhn
Aug 10, 2012·American Journal of Physiology. Renal Physiology·Yoshikazu MuroyaMasahiro Kohzuki

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