Urinary mRNA markers of epithelial–mesenchymal transition correlate with progression of diabetic nephropathy

Abstract

Epithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA (mRNA) expression in urinary sediment is emerging as a noninvasive method of screening DN-associated biomarkers. The aim of our study was to examine whether urinary mRNA profile of EMT-associated genes may provide valuable clinical insight into the different stages of DN. Diabetic nephropathy patients (n = 44) and healthy controls (n = 12) were enrolled in this study. DN patients were divided into three groups according to the levels of estimated glomerular filtration rate (eGFR): Group A (eGFR > 60 ml/min per 1·73 m(2), n = 27), Group B (45 < eGFR < 60 ml/min per 1·73 m(2), n = 9), and Group C (eGFR < 45 ml/min per 1·73 m(2), n = 8). Relative mRNA abundance of α-smooth muscle actin (α-SMA), fibronectin, FSP1 and matrix metalloproteinase-9 (MMP-9) were quantified, and correlations between target mRNAs and clinical parameters were examined. The urinary mRNA levels of α-SMA, fibronectin and MMP-9 were significantly higher in the DN group compared with controls (P < 0·05), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both urinary albumin excretion (UAE) and blood urea nitrogen (BUN). Moreover, the expression of α-SMA, fibronectin and MMP-9 mRNA correlated with serum creatinine levels (r = 0·514, r = 0·53 and r = 0·469, all P < 0·001) and GFR levels (r = -0·374, r = -0·392 and r = -0·487, all P < 0·01). Quantification of EMT-associated genes in urinary sediment may be a novel approach for searching new biomarkers of DN.