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

Melissa Uil, Chi M Hau, Mohamed Ahdi, James D Mills, Jesper Kers, Moin A Saleem, Sandrine Florquin, Victor E A Gerdes, Rienk Nieuwland, Joris J T H Roelofs

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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.

Original languageEnglish
Pages (from-to)358-365
Number of pages8
JournalClinical Kidney Journal
Volume14
Issue number1
Early online date23 Oct 2019
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.

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