Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation

• Published in: Cellular physiology and biochemistry Vol. 50; no. 3; pp. 1005 - 1014
• Main Authors: Rovira-Llopis, Susana, Escribano-Lopez, Irene, Diaz-Morales, Noelia, Iannantuoni, Francesca, Lopez-Domenech, Sandra, Andújar, Isabel, Jover, Ana, Pantoja, Jonay, Pallardo, Luis M., Bañuls, Celia, Victor, Victor M.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.10.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Aged; Albuminuria - etiology; Biomarkers; Biomarkers - blood; Cancer; Cardiovascular disease; Cell Adhesion; Cell adhesion & migration; Coronary vessels; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnosis; Diabetic Nephropathies - complications; Diabetic Nephropathies - diagnosis; Diabetic nephropathy; Diabetic neuropathy; Down-Regulation; Endocrinology; Endothelial Cells - cytology; Endothelial Cells - metabolism; Female; Gene expression; Glucose; Hospitals; Humans; Inflammation; Inflammation - pathology; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-6 - metabolism; Leukocyte-endothelial interaction; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Male; MicroRNAs; MicroRNAs - blood; Middle Aged; miRNAs; Nephropathy; Original Paper; Pathogenesis; Tumor Necrosis Factor-alpha - metabolism; Type 2 diabetes; Urine; Type 2 diabetes; Inflammation; Nephropathy; Leukocyte-endothelial interaction; miRNAs
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000494485

Background/Aims: There is a lack of reliable biological markers for the early diagnosis of diabetic nephropathy (DN) during type 2 diabetes. In this pilot study we aim to assess whether miR-31 levels are modulated by the presence of DN and whether the expression of this miRNA is related to leukocyte-endothelial interactions and inflammation. Methods: Thirty-one T2D patients were enrolled in this pilot study; 18 with no diabetic complications and 13 with diabetic nephropathy. 24 non-diabetic subjects and 13 T2D patients with retinopathy (absent of other complications) were included to test the specificity of miR-31. Following anthropometric and biochemical evaluation, serum miR-31 levels were assessed by Real Time-PCR. Leukocyte-endothelial interactions were evaluated by a parallel flow chamber in vitro model. Serum TNFα, IL-6 and ICAM-1 levels were determined by XMAP-technology in a flow cytometry-based Luminex 200 instrument. Results: Serum miR-31 levels were similar between control and T2D subjects. However, T2D patients with DN displayed reduced levels of miR-31 with respect to patients without complications. This decrease in miR-31 was more pronounced in patients with macroalbuminuria than in those with microalbuminuria and was specific for DN, since patients with retinopathy displayed unaltered miR-31 levels. The presence of DN involved a lower leukocyte rolling velocity and an increased rolling flux and adhesion. miR-31 levels were positively correlated with leukocyte rolling velocity and negatively associated to leukocyte adhesion, TNFα, IL-6 and ICAM-1 levels. Conclusion: Serum miR-31 may be a biomarker for DN in T2D patients. The regulation of this miRNA seems to be related to the recruitment of leukocytes to vascular walls induced by pro-inflammatory and adhesion molecules.