MiR-802 causes nephropathy by suppressing NF-κB-repressing factor in obese mice and human.

Obesity is associated with significant microvascular complications including renal injuries and may induce end-stage renal disease. Emerging studies have demonstrated microRNAs (miRNAs) are potential mediators in the pathophysiological process of nephropathy. The present study aimed to investigate the role of miR-802 in obesity-related nephropathy and potential molecular mechanisms. Through utilizing obese mouse model and human subjects, we explored the therapeutic benefits and clinical application of miR-802 in protecting against nephropathy. Renal miR-802 level was positively correlated with functional parameters, including blood urea nitrogen and creatinine in obese mice. Specific silencing of renal miR-802 improved high fat diet (HFD)-induced renal dysfunction, structural disorders and fibrosis. The up-regulated inflammatory response and infiltrated macrophages were also significantly decreased in miR-802 inhibitor-treated obese mice. Mechanistically, miR-802 directly bond to 3'-UTR of NF-κB-repressing factor (NRF) and suppressed its expression. In clinical study, the circulating miR-802 level was significantly increased in obese subjects, and positively correlated with plasma creatinine level but negatively correlated with creatinine clearance. Taken together, our findings provided evidence that miR-802/NRF signalling was an important pathway in mediating obesity-related nephropathy. It is a possible useful clinical approach of treating miR-802 inhibitor to combat nephropathy.

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