Urinary MiRNA-27b-3p and MiRNA-1228-3p Correlate with the Progression of Kidney Fibrosis in Diabetic Nephropathy

Overview

Journal Sci Rep

Specialty Science

Date 2019 Aug 8

PMID 31388051

Citations 52

Authors

Francesca Conserva

Mariagrazia Barozzino

Francesco Pesce

Chiara Divella

Annarita Oranger

Massimo Papale

Fabio Sallustio

Simona Simone

Luigi Laviola

Francesco Giorgino

Anna Gallone

Paola Pontrelli

Loreto Gesualdo

Affiliations

Soon will be listed here.

Abstract

Diabetic Nephropathy (DN) is a chronic complication of diabetes and the primary cause of end stage renal disease. Differential diagnosis for DN requires invasive histological investigation, thus there is need for non-invasive biomarkers to discriminate among different histological lesions in diabetic patients. With the aim to identify a pattern of differentially expressed miRNAs in kidney biopsies of DN patients, we assayed miRNA expression in kidney biopsies from DN patients, diabetic patients with membranous nephropathy and patients with normal histology. Nine miRNAs were differentially expressed among the three groups, and 2 miRNAs (miR-27b-3p and miR-1228-3p) showed interaction with an ubiquitin-conjugating E2 enzyme variant (UBE2v1). UBE2v1 mediates the formation of lysine 63-linked ubiquitin chains, a mechanism we previously showed as involved in DN kidney fibrosis. Both miRNAs were validated as down-regulated in biopsies and urines of DN patients, possibly affected by DNA methylation. Interestingly, the urinary levels of both miRNAs could also discriminate among different degrees of renal fibrosis. Finally, we showed that the combined urinary expression of both miRNAs was also able to discriminate DN patients from other glomerulonephritides in diabetic patients. In conclusion we identified two miRNAs potentially useful as candidate biomarkers of tubular-interstitial fibrosis in diabetic patients with DN.

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