The orphan nuclear receptor RORα is a potential endogenous protector in renal ischemia/reperfusion injury

Emerging evidence indicates that retinoid-related orphan receptor (ROR)α, a member of the ROR nuclear receptor 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 (WT) C57 black 6 (C57BL/6) mice and RORα-deficient stagger [ROR(sg/sg)] mice and their WT littermates were used for in vivo studies. The renal I/R injury model was induced by bilateral renal pedicle clamping for 35 min. Human proximal tubule cell line cells were treated with hypoxia (1% oxygen) to establish the cell hypoxia/reoxygenation (H/R) model. We investigated the renal expression and biologic function of RORα, and we found that RORα was significantly down-regulated after renal I/R injury. ROR(sg/sg) mice displayed dramatically augmented renal dysfunction and morphologic damage compared with WT mice at 24 h post-I/R. Further study revealed that the detrimental effects of RORα def...