ATF3-mediated epigenetic regulation protects against acute kidney injury

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

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1003-1013
Number of pages11
JournalJournal of the American Society of Nephrology
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 2010
Externally publishedYes

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Acute Kidney Injury
Epigenomics
Reperfusion Injury
Kidney
Histone Deacetylase 1
Genes
Interleukin-6
P-Selectin
Histones
Peroxidase
Chromatin
Reperfusion
Neutrophils
Up-Regulation
Ischemia
Apoptosis
Inflammation
Mortality

ASJC Scopus subject areas

  • Nephrology

Cite this

ATF3-mediated epigenetic regulation protects against acute kidney injury. / Li, Hsiao Fen; Cheng, Ching Feng; Liao, Wei Ju; Lin, Heng; Yang, Ruey Bing.

In: Journal of the American Society of Nephrology, Vol. 21, No. 6, 06.2010, p. 1003-1013.

Research output: Contribution to journalArticle

Li, Hsiao Fen ; Cheng, Ching Feng ; Liao, Wei Ju ; Lin, Heng ; Yang, Ruey Bing. / ATF3-mediated epigenetic regulation protects against acute kidney injury. In: Journal of the American Society of Nephrology. 2010 ; Vol. 21, No. 6. pp. 1003-1013.
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