Disruption of guanylyl cyclase-G protects against acute renal injury

Heng Lin, Ching Feng Cheng, Hsin Han Hou, Wei Shiung Lian, Ying Chi Chao, Yi Yun Ciou, Bambang Djoko, Ming Tzu Tsai, Chien Jui Cheng, Ruey Bing Yang

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25 Citations (Scopus)

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-κB were lower in GC-G -/- mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G-/- mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

Original languageEnglish
Pages (from-to)339-348
Number of pages10
JournalJournal of the American Society of Nephrology
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

Cite this

Lin, H., Cheng, C. F., Hou, H. H., Lian, W. S., Chao, Y. C., Ciou, Y. Y., Djoko, B., Tsai, M. T., Cheng, C. J., & Yang, R. B. (2008). Disruption of guanylyl cyclase-G protects against acute renal injury. Journal of the American Society of Nephrology, 19(2), 339-348. https://doi.org/10.1681/ASN.2007050550