Kidney injury molecule-1 protects against Gα12 activation and tissue damage in renal ischemia-reperfusion injury

The American Journal of Pathology
Ola Z IsmailLakshman Gunaratnam

Abstract

Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1(+/+) mice, Kim-1(-/-) mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1-deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibiti...Continue Reading

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Citations

Apr 17, 2016·Molecular and Cellular Biochemistry·Zhiwei Zhang, Cindy X Cai
Oct 21, 2016·Renal Failure·Caixia Yin, Ningning Wang
Feb 20, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Lei TianZhaohui Ni
Oct 13, 2016·Scientific Reports·Ryoichi SugisawaToru Miyazaki
Apr 1, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Ji Yun LeeLakshman Gunaratnam
Apr 26, 2018·Journal of Cellular Physiology·Ola Z IsmailLakshman Gunaratnam
Sep 9, 2017·Journal of Immunology Research·Zhu-Xu ZhangAnthony M Jevnikar
Jan 12, 2017·Clinical Chemistry and Laboratory Medicine : CCLM·Kianoush KashaniClaudio Ronco
Apr 28, 2018·Current Opinion in Nephrology and Hypertension·Sarah A StrausserTomokazu Souma
May 16, 2019·American Journal of Physiology. Renal Physiology·Yoei MiyabeTatsuya Shimizu
Dec 25, 2015·American Journal of Physiology. Renal Physiology·Ola Z IsmailLakshman Gunaratnam
Jul 30, 2020·International Journal of Toxicology·Miriam E Mossoba, Robert L Sprando
Apr 1, 2020·Cellular & Molecular Biology Letters·Mehri Bemani NaeiniAmirhossein Sahebkar
Jul 31, 2016·Acta Physiologica·E V SchrezenmeierK M Schmidt-Ott
Jan 28, 2020·American Journal of Physiology. Renal Physiology·Elena Tutunea-FatanLakshman Gunaratnam
Nov 20, 2020·Molecular and Cellular Biochemistry·Saranga SriranganathanLakshman Gunaratnam
Nov 30, 2019·Lancet·Claudio RoncoJohn A Kellum
Jun 6, 2021·Scientific Reports·Jasper C LeeLakshman Gunaratnam

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