| First Author | Wang W | Year | 2009 |
| Journal | Am J Pathol | Volume | 175 |
| Issue | 3 | Pages | 1010-8 |
| PubMed ID | 19700747 | Mgi Jnum | J:191562 |
| Mgi Id | MGI:5462043 | Doi | 10.2353/ajpath.2009.090224 |
| Citation | Wang W, et al. (2009) Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis. Am J Pathol 175(3):1010-8 |
| abstractText | Netrin-1, a diffusible laminin-related protein, is highly expressed in the kidney. However, the pathophysiological roles of netrin-1 in the kidney are unknown. To address this question directly, we used transgenic mice that overexpress chicken netrin-1 in the kidney. Netrin-1 overexpression was confirmed by real-time RT-PCR and Western blot analysis. Eight-week-old wild-type and transgenic mice were subjected to 26 minutes of renal ischemia followed by reperfusion for 72 hours. Wild-type mice developed more severe renal dysfunction by 24 hours than netrin-1 transgenic mice. Functional improvement was associated with better preservation of morphology, reduced cytokine expression, and reduced oxidative stress in the kidney of transgenic mice as compared with wild-type mice. In addition, both basal and reperfusion-induced cell proliferation were dramatically increased in transgenic kidneys as determined by Ki-67 staining. Interestingly, ischemia reperfusion induced a large increase in apoptosis in wild-type mice but not in netrin-1 transgenic mice that was associated with reduced caspase-3 activation in the transgenic kidney. These results suggest that netrin-1 protects renal tubular epithelial cells against ischemia reperfusion-induced injury by increasing proliferation and suppressing apoptosis. |
