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Bariatric surgery modulates urinary levels of microRNAs involved in the regulation of renal function

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Title: Bariatric surgery modulates urinary levels of microRNAs involved in the regulation of renal function
Authors: Gooderham, N
Alkandari, A
Ashrafian, H
Sathyapalan, T
Darzi, A
Holmes, E
Athanasiou, T
Atkin, S
Item Type: Journal Article
Abstract: Background: Obesity and diabetes cause chronic kidney disease with a common pathophysiology that is characterized by the accumulation of collagen in the extracellular matrix. Recent evidence has implicated the epithelial-to-mesenchymal transition (EMT) as a key step in this pathology with regulation by microRNAs. Weight loss leads to improvements in renal function; therefore, this study hypothesized that bariatric-surgery aided weight loss would lead to changes in urinary microRNAs involved in the regulation of renal function. Materials and methods: Twenty-four bariatric patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy donated urine pre-operatively and at 2–6 months and 1–2 years post-operatively. Urine samples were also obtained from 10 healthy weight and 7 morbidly obese non-surgical controls. Expression levels of kidney microRNAs were assessed in urine and the function of microRNAs was assessed through the in vitro transfection of HK-2 cells, a kidney proximal tubule cell line. Results: Levels of miR 192, miR 200a, and miR 200b were upregulated in urine following bariatric surgery. This increase was consistent across surgical type and diabetes status and was maintained and enhanced with time. Bariatric surgery alters urinary miR 192 expression from levels seen in morbidly obese patients to levels seen in healthy weight control patients. In mechanistic studies, the transfection of miR 192 in HK-2 cells increased miR 200a expression and decreased ZEB2, a key transcriptional promoter of kidney fibrosis. Conclusions: Bariatric surgery increased miR 192 and miR 200 urinary levels, key anti-fibrotic microRNAs that could contribute to a renal-protective mechanism and may be of value as urinary biomarkers following surgery. These findings suggest that urinary microRNAs may represent potential novel biomarkers for obesity-associated renal function.
Issue Date: 21-May-2019
Date of Acceptance: 2-May-2019
URI: http://hdl.handle.net/10044/1/70422
DOI: https://dx.doi.org/10.3389/fendo.2019.00319
ISSN: 1664-2392
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Endocrinology
Volume: 10
Copyright Statement: © 2019 Alkandari, Ashrafian, Sathyapalan, Darzi, Holmes, Athanasiou, Atkin and Gooderham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: National Institute of Health Research
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
microRNA
nephropathy
bariatric/metabolic surgery
urinary
longitudinal
diabetes
EPITHELIAL-MESENCHYMAL TRANSITION
CHRONIC KIDNEY-DISEASE
ROUX-EN-Y
WEIGHT-LOSS
DIABETIC-NEPHROPATHY
MIR-200 FAMILY
CIRCULATING MICRORNAS
COLLAGEN EXPRESSION
METABOLIC SURGERY
REPRESSORS ZEB1
Publication Status: Published
Article Number: ARTN 319
Appears in Collections:Division of Surgery



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