| First Author | Li HF | Year | 2010 |
| Journal | J Am Soc Nephrol | Volume | 21 |
| Issue | 6 | Pages | 1003-13 |
| PubMed ID | 20360311 | Mgi Jnum | J:185837 |
| Mgi Id | MGI:5430276 | Doi | 10.1681/ASN.2009070690 |
| Citation | Li HF, et al. (2010) ATF3-mediated epigenetic regulation protects against acute kidney injury. J Am Soc Nephrol 21(6):1003-13 |
| abstractText | 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-kappaB 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-kappaB 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. |
