Cellular origin and microRNA profiles of circulating extracellular vesicles in different stages of diabetic nephropathy

Abstract Background Diabetic nephropathy (DN) is a major complication of diabetes and the main cause of end-stage renal disease. Extracellular vesicles (EVs) are small cell-derived vesicles that can alter disease progression by microRNA (miRNA) transfer. Methods In this study, we aimed to characteri...

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Bibliographic Details
Published in:Clinical Kidney Journal 2021-01, Vol.14 (1), p.358-365
Main Authors: Uil, Melissa, Hau, Chi M, Ahdi, Mohamed, Mills, James D, Kers, Jesper, Saleem, Moin A, Florquin, Sandrine, Gerdes, Victor E A, Nieuwland, Rienk, Roelofs, Joris J T H
Format: Article
Language:English
Subjects:
Chronic kidney failure
Development and progression
Diabetic nephropathies
Diabetics
MicroRNA
Original
Type 2 diabetes
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Summary:Abstract Background Diabetic nephropathy (DN) is a major complication of diabetes and the main cause of end-stage renal disease. Extracellular vesicles (EVs) are small cell-derived vesicles that can alter disease progression by microRNA (miRNA) transfer. Methods In this study, we aimed to characterize the cellular origin and miRNA content of EVs in plasma samples of type 2 diabetes patients at various stages of DN. Type 2 diabetes patients were classified in three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. The concentration and cellular origin of plasma EVs were measured by flow cytometry. A total of 752 EV miRNAs were profiled in 18 subjects and differentially expressed miRNAs were validated. Results Diabetic patients with microalbuminuria and/or macroalbuminuria showed elevated concentrations of total EVs and EVs from endothelial cells, platelets, leucocytes and erythrocytes compared with diabetic controls. miR-99a-5p was upregulated in macroalbuminuric patients compared with normoalbuminuric and microalbuminuric patients. Transfection of miR-99a-5p in cultured human podocytes downregulated mammalian target of rapamycin (mTOR) protein expression and downregulated the podocyte injury marker vimentin. Conclusions Type 2 diabetes patients with microalbuminuria and macroalbuminuria display differential EV profiles. miR-99a-5p expression is elevated in EVs from macroalbuminuria and mTOR is its validated mRNA target.
ISSN:2048-8505
2048-8513
DOI:10.1093/ckj/sfz145