Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients

Abstract

MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of diabetic nephropathy. miRNAs are present in urine in a remarkably stable form packaged in extracellular vesicles, predominantly exosomes. In the present study, urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from 8 healthy controls (C), 8 patients with type II diabetes (T2D) and 8 patients with type II diabetic nephropathy (DN) using Agilent´s miRNA microarrays. In total, the expression of 16 miRNA species was deregulated (>2-fold) in DN patients compared to healthy donors and T2D patients: the expression of 14 miRNAs (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p and miR-2861) was up-regulated whereas the expression of 2 miRNAs (miR-30d-5p and miR-30e-5p) was down-regulated. Most of the deregulated miRNAs are involved in progression of renal diseases. Deregulation of urinary exosomal miRNAs occurred in micro-albuminuric DN patients but not in normo-albuminuric DN patients. We used qRT-PCR based analysis of the most strongly up-regulated miRNAs in urinary exosomes from DN patients, miRNAs miR-320c and miR-6068. The correlation of miRNA expression and micro-albuminuria levels could be replicated in a confirmation cohort. In conclusion, urinary exosomal miRNA content is altered in type II diabetic patients with DN. Deregulated miR-320c, which might have an impact on the TGF-β-signaling pathway via targeting thrombospondin 1 (TSP-1) shows promise as a novel candidate marker for disease progression in type II DN that should be evaluated in future studies.

Regulatory Roles of MicroRNAs in Diabetes

“…Interestingly, another type of miRNA that may serve as a candidate marker for DN is urinary miRNAs. Aberrant urinary miR-320c , isolated from urinary exosomes, may impact the TGF-β signaling pathway via targeting THBS1 and could be used as a novel candidate marker for disease progression in DN [69]. …”

New insights on microRNAs in diabetic nephropathy: potential biomarkers for diagnosis and therapeutic targets

“…Недавно были опубликованы результаты пилотного исследования изменения профиля экзосомальных ми-кроРНК в моче у больных СД2 [55]. Авторы обнаружили, что у пациентов с ДН по сравнению со здоровыми доно-рами и больными СД2 без ДН экспрессия 14 микроРНК (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p и miR-2861) была повышена (более чем в 2 раза), а 2 микроРНК (miR-30d-5p и miR-30e-5p) -снижена.…”

Uromodulin mRNA from Urinary Extracellular Vesicles Correlate to Kidney Function Decline in Type 2 Diabetes Mellitus

“…In the last 5 years, microRNA, a class of small non-coding RNAs, has emerged as additional potential diagnostic and prognostic biomarkers in renal diseases. Altered miRNA profiles including transforming growth factor-β1-regulated plasma miRNAs, let-7b-5p and miR-21–5p, and urinary exosomal miR-320c have been associated with different stages of DKD [10, 11]. …”