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

研究成果: 雜誌貢獻文章

25 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)339-348
頁數10
期刊Journal of the American Society of Nephrology
19
發行號2
DOIs
出版狀態已發佈 - 二月 2008
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Nephrology

引用此

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