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Kidney Week

Abstract: TH-OR005

The Orphan Nuclear Receptor RORα Is a Potential Endogenous Protector in Renal Ischemia/Reperfusion Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Cai, Jieru, Zhongshan Hospital, Fudan University, Shanghai, China

Emerging evidence indicates that retinoid-related orphan receptor alpha (RORα), a member of the ROR nuclear receptor (NR) subfamily, mediates key cellular adaptions to hypoxia and contributes to the pathophysiology of many disease states. However, the effects of RORα in renal ischemia/reperfusion (I/R) injury remain unclear.


Wild-type C57BL/6 mice, ROR-deficient stagger [ROR (sg/sg)] mice and their wild-type (WT) littermates were used for in vivo studies. Renal I/R injury model was induced by bilateral renal pedicle clamping for 35 minutes. HK-2 cells and human kidney samples were used for in vitro studies. HK-2 cells were treated with hypoxia (1% oxygen) to establish the cell hypoxia/reoxygenation (H/R) model.


We found that RORα was significantly down-regulated after renal I/R injury. RORα-deficient stagger mice displayed dramatically augmented renal dysfunction and morphological damage compared with wild-type (WT) mice at 24 hours post-I/R. Further study revealed that the detrimental effects of RORα deficiency were attributable to tubular epithelial cell apoptosis and, consequently, renal inflammation and oxidative stress. The proapoptotic effect of RORα deficiency was associated with aggravated mitochondrial dysfunction in renal tubular cells after I/R. However, pretreatment of WT mice with the RORα agonist SR1078 ameliorated I/R-induced renal dysfunction and damage and elicited a concomitant decrease in tubular epithelial cell apoptosis.


In summary, our study provides experimental evidence showing that RORα is a novel endogenous protector against renal I/R injury and that RORα activation is a promising therapeutic strategy for the prevention of acute kidney injury.

RORα deficiency aggravates renal injury at 24 hours post-I/R.


  • Government Support - Non-U.S.