| Autor: |
Dimuccio V; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10124 Turin, Italy., Bellucci L; Laboratory of Translational Research in Paediatric Nephro-Urology, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy., Genta M; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10124 Turin, Italy., Grange C; Department of Medical Sciences, University of Turin, 10124 Turin, Italy., Brizzi MF; Department of Medical Sciences, University of Turin, 10124 Turin, Italy., Gili M; Department of Medical Sciences, University of Turin, 10124 Turin, Italy., Gallo S; Department of Medical Sciences, University of Turin, 10124 Turin, Italy., Centomo ML; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10124 Turin, Italy., Collino F; Laboratory of Translational Research in Paediatric Nephro-Urology, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy.; Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy., Bussolati B; Department of Molecular Biotechnology and Health Sciences, University of Turin, 10124 Turin, Italy. |
| Abstrakt: |
Diabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney's physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition. |
