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

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

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
DOIs
Publication statusPublished - Jan 2021

Keywords

  • diabetic kidney disease
  • diabetic nephropathy
  • extracellular vesicles
  • mTOR
  • miRNA
  • podocytes

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