ATF3 protects against renal ischemia-reperfusion injury

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

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

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. H2O 2 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 H 2O2-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.

Original languageEnglish (US)
Pages (from-to)217-224
Number of pages8
JournalJournal of the American Society of Nephrology
Volume19
Issue number2
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Nephrology

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    Yoshida, T., Sugiura, H., Mitobe, M., Tsuchiya, K., Shirota, S., Nishimura, S., Shiohira, S., Ito, H., Nobori, K., Gullans, S. R., Akiba, T., & Nitta, K. (2008). ATF3 protects against renal ischemia-reperfusion injury. Journal of the American Society of Nephrology, 19(2), 217-224. https://doi.org/10.1681/ASN.2005111155