RETRACTED: BMSCs-derived exosomal microRNA-let-7a plays a protective role in diabetic nephropathy via inhibition of USP22 expression

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. The molecular pathogenesis of DN is still poorly understood. This study was designed to investigate the protective effect of bone marrow mesenchymal stem cell (BMSCs)-derived exosome (Exo)-transported microRNA-let-7a (miR-let-7a) on DN by targeting ubiquitin-specific protease 22 (USP22). BMSCs of rats were cultured, and exosomes were identified. A rat models of DN were established in this study, and the rats were injected with Exo, Exo-let-7a mimic, or si-USP22 to figure their functions in renal function indicators blood urea nitrogen (BUN) and serum creatinine (SCr), blood lipid-related indicators total cholesterol (TC) and triglyceride (TG), renal cell apoptosis, oxidative stress, and expression of N-cadherin and vimentin in renal tissues. MiR-let-7a and USP22 targeting relationship was validated. Suppressed miR-let-7a and over-expressed USP22 exhibited in renal tissues of DN rats. Exosomes increased miR-let-7a and repressed USP22 in renal tissues of DN rats. Moreover, elevated exosomal miR-let-7a or silenced USP22 reduced SCr, BUN, TG and TC, suppressed apoptosis of renal cells and oxidative stress, and inhibited N-cadherin and vimentin expression in renal tissues of DN rats. MiR-let-7a had a targeting relationship with USP22. Our study highlights that BMSCs-derived exosomal miR-let-7a represses renal cell apoptosis, which plays a protective role in DN through down-regulation of USP22.