Urinary exosomal microRNAs in incipient diabetic nephropathy.
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.
Diabetic Nephropathy Laboratory, Department of Medical Science, University of Turin, Turin, Italy.
Federica
F
Barutta
Marinella
M
Tricarico
Alessandro
A
Corbelli
Laura
L
Annaratone
Silvia
S
Pinach
Serena
S
Grimaldi
Graziella
G
Bruno
Daniela
D
Cimino
Daniela
D
Taverna
Maria Chiara
MC
Deregibus
Maria Pia
MP
Rastaldi
Paolo Cavallo
PC
Perin
Gabriella
G
Gruden
D000419:Albuminuria / Q000652:urine*; D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine*; D055354:Exosomes / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000652:urine*; D008875:Middle Aged; D015854:Up-Regulation
C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D005947:Glucose