microRNA-199a downregulation alleviates hyperuricemic nephropathy via the PPAR gamma/beta-catenin axis

Hyperuricemia always develops into hyperuricemic nephropathy (HN). The role of microRNA (miR) in HN is less studied. We aimed to discuss the role of miR-199a in HN. The expression of miR-199a and PPAR gamma in renal tissues of HN rats was detected. The targeting relation between miR-199a and PPAR gamma was verified. The contents of SCr, UA, BUN, and mALB, renal injury-relevant biomarkers were detected, and the pathological changes of renal tissue and renal interstitial fibrosis were observed by histological staining. After miR-199a and PPAR gamma knockdown, the contents of SCr, BUN, and mALB and renal interstitial fibrosis were estimated. Collectively, overexpression of miR-199a aggravated the renal injury in HN rats. By contrast, inhibition of miR-199a weakened renal injury, as evidenced by decreased contents of SCr, UA, BUN, and mALB, and mitigated renal interstitial fibrosis. miR-199a targeted PPAR gamma. Silencing of PPAR gamma upregulated the levels of downstream genes of beta-catenin and the contents of SCr, UA, BUN, and mALB and deteriorated renal interstitial fibrosis. Moreover, the silencing of PPAR gamma blocked the alleviative effects of miR-199a inhibitor on the renal injury. Overall, miR-199a targets PPAR gamma and activates the beta-catenin pathway, thus aggravating HN, which might provide a future target for the treatment of HN.