Urinary exosomal microRNAs in incipient diabetic nephropathy

早期糖尿病肾病中的尿液外泌体微小RNA

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作者:Federica Barutta, Marinella Tricarico, Alessandro Corbelli, Laura Annaratone, Silvia Pinach, Serena Grimaldi, Graziella Bruno, Daniela Cimino, Daniela Taverna, Maria Chiara Deregibus, Maria Pia Rastaldi, Paolo Cavallo Perin, Gabriella Gruden

Abstract

MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Results showed that miR-130a and miR-145 were enriched, while miR-155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria. Similarly, in an animal model of early experimental diabetic nephropathy, urinary exosomal miR-145 levels were increased and this was paralleled by miR-145 overexpression within the glomeruli. Exposure of cultured mesangial cells to high glucose increased miR-145 content in both mesangial cells and mesangial cells-derived exosomes, providing a potential mechanism for diabetes-induced miR-145 overexpression. In conclusion, urinary exosomal miRNA content is altered in type 1 diabetic patients with incipient diabetic nephropathy and miR-145 may represent a novel candidate biomarker/player in the complication.

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