Urinary Exosomal MiRNA-4534 as a Novel Diagnostic Biomarker for Diabetic Kidney Disease.

Yanyan Zhao,Mengxing Pan,Na Jing,Feng Guo,Xiaoxu Ding,Haohao Zhang,Lina Wu,Guijun Qin,Xiaojun Ma,Ao Shen,Jiao Wang,Liang Feng,Yi Song

doi:10.3389/fendo.2020.00590

Abstract

Urinary exosomal miRNAs can reflect the physiological and possibly pathophysiological state of cells lining the kidney and participate in the regulation of transcription and translation of proteins, which are playing an important role in the pathogenesis of diabetic kidney disease. In the present study, urine was collected from DM and DKD patients with a duration more than 10 years and urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from three patients with type 2 diabetes (DM) and three patients with type 2 diabetic kidney disease (DKD) using Exiqon's microRNA arrays. In total, the expression of 14 miRNAs (miR-4491, miR-2117, miR-4507, miR-5088-5P, miR-1587, miR-219a-3p, miR-5091, miR-498, miR-4687-3p, miR-516b-5p, miR-4534, miR-1275, miR-5007-3p, and miR-4516) was up-regulated (>2-fold) in DKD patients compared to healthy controls and DM patients. We used qRT-PCR based analysis of these 14 miRNAs in urinary exosomes from 14 DKD to 14 DM patients in confirmation cohort, among which seven miRNAs were consistent with the microarray results. The expressions of miR-4534 and miR-516b-5p correlated with trace proteinuria levels in the confirmation cohort. In conclusion, it has been confirmed that the expression of urinary exosomal miRNA in patients with type 2 diabetes DKD has changed. Mir-4534 might affect the FoxO signaling pathway by targeting BNIP3, and is expected to become a new biomarker for the progression of type 2 DKD disease, which will provide further research on the pathogenesis of DKD.

Highlights

Diabetic kidney disease (DKD) is a common cause of end-stage renal disease (ESRD) worldwide, but the true incidence and prevalence of ESKD from diabetes is impossible to know because kidney biopsies [the gold standard for diagnosis of diabetic kidney disease [1]] are infrequently performed in diabetic patients with diabetic kidney disease [2]
Recent studies suggested that urinary exosomal miRNAs, recognized a kind of potential non-invasive biomarker for early diagnosis and therapy of DKD, can help us understand the pathophysiological mechanisms leading to renal damage [4]
According to the results of urinary exosomal microarray, a total of 2,085 miRNA were detectable from DKD patients (Fold change > 5, P < 0.05, Figures 2, 3). 326 miRNAs showed significant upregulation in the exosomes of DKD group compared to DM group

Summary

Introduction

Diabetic kidney disease (DKD) is a common cause of end-stage renal disease (ESRD) worldwide, but the true incidence and prevalence of ESKD from diabetes is impossible to know because kidney biopsies [the gold standard for diagnosis of diabetic kidney disease [1]] are infrequently performed in diabetic patients with diabetic kidney disease [2]. Some conditions, including exercise within 24 h, high-protein diet, infection, and fever, might result in falsely elevated albuminuria without any kidney damages [3]. These markers are usually a late sign of kidney damage. Recent studies suggested that urinary exosomal miRNAs, recognized a kind of potential non-invasive biomarker for early diagnosis and therapy of DKD, can help us understand the pathophysiological mechanisms leading to renal damage [4]

Methods

Results

Conclusion