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1664-2392102019Frontiers in endocrinologyFront Endocrinol (Lausanne)Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function.31931931910.3389/fendo.2019.00319Background: 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.AlkandariAbdullahADepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.Dasman Diabetes Institute, Kuwait City, Kuwait.AshrafianHutanHDepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.Institute of Global Health Innovation, Imperial College London, London, United Kingdom.SathyapalanThozhukatTDepartment of Academic Endocrinology, Diabetes, and Metabolism, Hull York Medical School, Kingston upon Hull, United Kingdom.DarziAraADepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.Institute of Global Health Innovation, Imperial College London, London, United Kingdom.HolmesElaineEDepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.AthanasiouThanosTDepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.AtkinStephen LSLWeill Cornell Medical College Qatar, Qatar Foundation, Doha, Qatar.GooderhamNigel JNJDepartment of Surgery and Cancer, Imperial College London, London, United Kingdom.engJournal Article20190521
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