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ATF3 Protects against Renal Ischemia-Reperfusion Injury

By Takumi Yoshida, Hidekazu Sugiura, Michihiro Mitobe, Ken Tsuchiya, Satsuki Shirota, Sayoko Nishimura, Shunji Shiohira, Hiroshi Ito, Kiyoshi Nobori, Steven R. Gullans, Takashi Akiba and Kosaku Nitta


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), p21WAF1/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

Topics: Basic Research
Publisher: American Society of Nephrology
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Provided by: PubMed Central
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