| Summary: | 碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 96 === Renal ischemia/reperfusion (I/R) is a common cause of acute renal failure (ARF). Apoptosis and inflammation are core mechanisms leading to organ damage in the course of renal I/R. Activating transcription factor 3 (ATF3), a stress inducible transcription factor, was rapidly induced by renal I/R in the mouse animal model. We used ATF3 knockout mice to figure out the role of ATF3 in the renal I/R injury. According to the data, ATF3 upregulated in the nuclei of tubule cells post 3 hours of renal I/R injury. Under renal I/R condition, ATF3 knockout mice suffered severe renal dysfunction, neutrophil infiltration,
adhesion molecules expression, tubule cells apoptosis and had lower survival rate compared with wild-type mice. When ATF3 was overexpression in NRK-52E (rat tubule cells) cells via adenovirus-mediated gene transfer, hypoxia/ reoxygenation-induced apoptosis was reduced. In addition, adenovirus-mediated expression of ATF3 inhibited NF-kB activated luciferase activity of IL-12 promoter. What is more, ATF3 bind to the ATF/CRE site on the P-selectin promoter and suppressed its expression. In conclusion, ATF3 plays a protective role in renal I/R injury and the mechanism of the protection may involve suppression of IL-12 and P-selectin expression.
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