MicroRNAs from urinary extracellular vesicles are non-invasive early biomarkers of diabetic nephropathy in type 2 diabetes patients with the ‘Asian Indian phenotype’

Autor: Sophie Rome, Viswanathan Mohan, Caroline Gastebois, Emmanuelle Meugnier, Chandrakumar Sathishkumar, Paramasivam Prabu, Muthuswamy Balasubramanyam
Přispěvatelé: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Madras Diabetes Research Foundation, Partenaires INRAE, French-Indian Medical Research Co-operation (INSERM - ICMR PROGRAM, 2014-2017), Department of Biotechnology (DBT) India Government of India, meugnier, emmanuelle
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Journal of Diabetes & Metabolism
Journal of Diabetes & Metabolism, OMICS International, 2018
Diabetes and Metabolism
Diabetes and Metabolism, Elsevier Masson, 2019, 45 (3), pp.276-285. ⟨10.1016/j.diabet.2018.08.004⟩
ISSN: 2155-6156
1262-3636
Popis: In Press, Corrected Proof; International audience; Aims. – MicroRNAs (miRNAs) from extracellular vesicles (EVs) have been proposed as promising biomarkers for a number of diseases. In this study, their potential as urine-based biomarkers of diabetic nephropathy (DN) was assessed. Methods. – MiRNAs were profiled in urinary EVs from 160 fasting subjects with normal glucose tolerance (NGT) and in T2DM patients with either microalbumininuria (MIC) or macroalbuminuria (MAC). Results. – A total of 73 miRNAs detected in urinary EVs (NGT) were predicted to target important functions for kidney homoeostasis, thereby validating their use as indicators of kidney dysfunction. Indeed, a urinary EV miRNA signature was found to comprise increased levels of let-7i-3p, miR-24-3p and miR-27b-3p, and decreased levels of miR-15b-5p, to identify patients with MIC. ROC curve analysis confirmed this ability to identify MIC in normo-albuminuria T2DM (T2DM-NA) patients and to differentiate between MAC and T2DM patients. These miRNAs were also predicted to target protein networks involved in the Wnt/b-catenin signalling cascade, activin receptor signalling and cell differentiation/proliferation, and correlated with eGRF, HbA1c, serum creatinine, urea, albumin and blood pressure. Concentrations of miR-30a-5p were specifically modified in urinary EVs from patients with MAC, but not MIC, suggesting that miR-30a-5p could be related to severe kidney damage. Conclusion. – Urinary EV miRNAs correlate with the degree of MIC. As they are also thought to regulate pathways that are targets of pharmacological agents to prevent DN (reticulum stress, activin receptors), they may also serve as non-invasive ‘liquid biopsies’ to stratify patients at risk of developing MAC and to monitor treatment efficacy.
Databáze: OpenAIRE
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