期刊
LIFE SCIENCES
卷 268, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118937
关键词
Diabetic nephropathy; Bone marrow mesenchymal stem cells; Exosome; microRNA-let-7a; Ubiquitin-specific protease 22; Apoptosis
The study showed that BMSCs-derived exosomal miR-let-7a can protect against diabetic nephropathy by repressing renal cell apoptosis through downregulating USP22.
Objective: 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). Methods: 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. Results: 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. Conclusion: 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.
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