Urinary Exosomal MicroRNAs in Incipient Diabetic Nephropathy

被引:279
作者
Barutta, Federica [1 ]
Tricarico, Marinella [1 ]
Corbelli, Alessandro [2 ,3 ,4 ]
Annaratone, Laura [5 ]
Pinach, Silvia [1 ]
Grimaldi, Serena [1 ]
Bruno, Graziella [1 ]
Cimino, Daniela [6 ]
Taverna, Daniela [6 ]
Deregibus, Maria Chiara [7 ]
Rastaldi, Maria Pia
Perin, Paolo Cavallo [1 ]
Gruden, Gabriella [1 ]
机构
[1] Univ Turin, Dept Med Sci, Diabet Nephropathy Lab, Turin, Italy
[2] Osped Maggiore Policlin, Fdn IRCCS, Renal Res Lab, Milan, Italy
[3] Fdn DAmico Ric Malattie Renali, Milan, Italy
[4] Milano Bicocca Univ, MIA Consortium Image Anal, Milan, Italy
[5] Univ Turin, Dept Biomed Sci & Human Oncol, I-10124 Turin, Italy
[6] Univ Turin, Ctr Mol Biotechnol, Turin, Italy
[7] Univ Turin, Dept Med Sci, Lab Renal & Vasc Pathophysiol, Turin, Italy
关键词
KIDNEY GLOMERULI; EXPRESSION; CELLS; MICROALBUMINURIA; TGF-BETA-1; MIR-145; PLASMA;
D O I
10.1371/journal.pone.0073798
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:8
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