ATF3-mediated epigenetic regulation protects against acute kidney injury

Hsiao Fen Li, Ching Feng Cheng, Wei Ju Liao, Heng Lin, Ruey Bing Yang

研究成果: 雜誌貢獻文章同行評審

72 引文 斯高帕斯(Scopus)

摘要

A variety of stress stimuli, including ischemia-reperfusion (I/R) injury, induce the transcriptional repressor ATF3 in the kidney. The functional consequences of this upregulation in ATF3 after renal I/R injury are not well understood. Here, we found that ATF3-deficient mice had higher renal I/R-induced mortality, kidney dysfunction, inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin), and apoptosis compared with wild-type mice. Furthermore, gene transfer of ATF3 to the kidney rescued the renal I/R-induced injuries in the ATF3-deficient mice. Molecular and biochemical analysis revealed that ATF3 interacted directly with histone deacetylase 1 (HDAC1) and recruited HDAC1 into the ATF/NF-κB sites in the IL-6 and IL-12b gene promoters. The ATF3-associated HDAC1 deacetylated histones, which resulted in the condensation of chromatin structure, interference of NF-κB binding, and inhibition of inflammatory gene transcription after I/R injury. Taken together, these data demonstrate epigenetic regulation mediated by the stress-inducible gene ATF3 after renal I/R injury and suggest potential targeted approaches for acute kidney injury.

原文英語
頁(從 - 到)1003-1013
頁數11
期刊Journal of the American Society of Nephrology
21
發行號6
DOIs
出版狀態已發佈 - 6月 2010
對外發佈

ASJC Scopus subject areas

  • 腎臟病學

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