Urinary Exosomal MicroRNAs in Incipient Diabetic Nephropathy

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.

Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation

“…In this regard, microRNA (miRNA)-145 expression in urinary exosomes was greater in patients with type 1 diabetes compared to the control subjects. Exosomal miRNA-145 expression was also greater in an animal model of early experimental diabetic nephropathy (31).…”

Extracellular Vesicles in Renal Diseases

“…Differential miRNA profiling in uEXs was used to identify miRNAs that can differentiate patients with type 1 diabetes with and without DN. 86 Of 226 miRNAs, 22 miRNAs differed in matched pairs of patients with microalbuminuria and patients with normoalbuminuria. miRNA145 and miRNA130 were enriched in patients with microalbuminuria.…”

microRNAs in Diabetic Kidney Disease

“…A recent present study of assessment about microRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy demonstrates that miR-130a and miR-145 were enriched, while miR-155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria [108]. Interestingly, the increase of urinary exosomal miR-145 levels in an animal model of early experimental diabetic nephropathy is paralleled by miR-145 overexpression within the glomeruli [108]. Treatment with high glucose in cultured MC also upregulates miR-145 levels in both MCs and MCderived exosomes, suggesting a correlation between circulating microRNA and its renal expression during DN.…”