6533b86ffe1ef96bd12cd4ce

RESEARCH PRODUCT

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

Irene Escribano-lopezJonay PantojaIsabel AndújarCelia BañulsAna JoverSusana Rovira-llopisVictor M. VictorSandra López-domènechLuis M PallardóNoelia Diaz-moralesFrancesca Iannantuoni

subject

Male0301 basic medicinemedicine.medical_specialtyPhysiologyDown-RegulationInflammationType 2 diabeteslcsh:PhysiologyNephropathylcsh:BiochemistryDiabetic nephropathy03 medical and health sciences0302 clinical medicineInternal medicineCell AdhesionmedicineAlbuminuriaHumanslcsh:QD415-436Diabetic NephropathiesAgedInflammationlcsh:QP1-981Interleukin-6Tumor Necrosis Factor-alphabusiness.industryEndothelial CellsType 2 diabetesMiddle AgedIntercellular Adhesion Molecule-1medicine.diseaseNephropathymir-31MicroRNAs030104 developmental biologyEndocrinologyDiabetes Mellitus Type 2030220 oncology & carcinogenesismiRNAsLeukocytes MononuclearBiomarker (medicine)Leukocyte-endothelial interactionFemaleMicroalbuminuriamedicine.symptombusinessBiomarkersRetinopathy

description

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.

https://doi.org/10.1159/000494485