| First Author | Yoshida T | Year | 2008 |
| Journal | J Am Soc Nephrol | Volume | 19 |
| Issue | 2 | Pages | 217-24 |
| PubMed ID | 18235102 | Mgi Jnum | J:149928 |
| Mgi Id | MGI:3849380 | Doi | 10.1681/ASN.2005111155 |
| Citation | Yoshida T, et al. (2008) ATF3 protects against renal ischemia-reperfusion injury. J Am Soc Nephrol 19(2):217-24 |
| abstractText | Oxidative stress-induced cell death plays a major role in the progression of ischemic acute renal failure. Using microarrays, we sought to identify a stress-induced gene that may be a therapeutic candidate. Human proximal tubule (HK2) cells were treated with hydrogen peroxide (H2O2) and RNA was applied to an Affymetrix gene chip. Five genes were markedly induced in a parallel time-dependent manner by cluster analysis, including activating transcription factor 3 (ATF3), p21(WAF1/CiP1) (p21), CHOP/GADD153, dual-specificity protein phosphatase, and heme oxygenase-1. H2O2 rapidly induced ATF3 approximately 12-fold in HK2 cells and approximately 6.5-fold in a mouse model of renal ischemia-reperfusion injury. Adenovirus-mediated expression of ATF3 protected HK2 cells against H2O2-induced cell death, and this was associated with a decrease of p53 mRNA and an increase of p21 mRNA. Moreover, when ATF3 was overexpressed in mice via adenovirus-mediated gene transfer, ischemia-reperfusion injury was reduced. In conclusion, ATF3 plays a protective role in renal ischemia-reperfusion injury and the mechanism of the protection may involve suppression of p53 and induction of p21. |
