Orphan nuclear receptor Nur77 promotes acute kidney injury and renal epithelial apoptosis.

Journal of the American Society of Nephrology : JASN
Savithri BalasubramanianTerry B Strom

Abstract

Nur77 and its family members Nurr1 and Nor-1 are inducible orphan nuclear receptors that orchestrate cellular responses to diverse extracellular signals. In epithelia, Nur77 can act as a potent proapoptotic molecule in response to cellular stress, suggesting a possible role for this nuclear receptor in the tissue response to injury. Here, we found that Nur77 promotes epithelial cell apoptosis after AKI. Injury of proximal tubular epithelial cells rapidly and strongly induced Nur77, Nor-1, and Nurr1 both in vitro and in vivo. After renal ischemia-reperfusion, Nurr77-deficient mice exhibited less apoptosis of tubular epithelial cells and better renal function than wild-type mice. Nur77-mediated renal injury involved a conformational change of Bcl2 and an increase in the protein levels of proapoptotic Bcl-xS. Ligand-activated retinoic acid receptors repressed Nur77 induction and function. Pretreatment of wild-type mice with retinoic acid before renal ischemia-reperfusion blunted the induction of Nur77, conferred protection of renal function, attenuated renal histologic injury, and reduced the expression of epithelial-derived proinflammatory cytokines. Retinoic acid also inhibited hypoxia-mediated induction of proinflammatory cytok...Continue Reading

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Citations

Dec 13, 2012·Science Signaling·Savithri BalasubramanianTerry B Strom
Sep 21, 2012·American Journal of Physiology. Renal Physiology·Qingqing Wei, Zheng Dong
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Apr 12, 2014·Journal of the American Society of Nephrology : JASN·Lindsey WestbrookMichael R Garrett
Aug 5, 2017·Journal of the American Society of Nephrology : JASN·Satya K KotaSavithri Balasubramanian Kota
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Sep 15, 2020·The Journal of Clinical Investigation·Qingqing Wei, Zheng Dong
Jul 29, 2020·Frontiers in Pharmacology·Junxia WuChangchun Cao
Oct 11, 2012·Journal of Receptor and Signal Transduction Research·Tian-Biao Zhou, Yuan-Han Qin
Feb 15, 2021·Ecotoxicology and Environmental Safety·Yingchun ZhangZhixian Gao
Mar 2, 2021·American Journal of Physiology. Renal Physiology·Anqun ChenJohn Cijiang He

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