| First Author | Ismail OZ | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 5 | Pages | 1207-15 |
| PubMed ID | 25759266 | Mgi Jnum | J:220688 |
| Mgi Id | MGI:5635943 | Doi | 10.1016/j.ajpath.2015.02.003 |
| Citation | Ismail OZ, et al. (2015) Kidney Injury Molecule-1 Protects against Galpha12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury. Am J Pathol 185(5):1207-15 |
| abstractText | Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein alpha12 (Galpha12) 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 Galpha12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Galpha12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Galpha12. Compared with Kim-1(+/+) mice, Kim-1(-/-) mice exhibited greater Galpha12 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 inhibition of Galpha12. |
