Expression of miR-155, miR-146a, and miR-326 in T1D patients from Chile: relationship with autoimmunity and inflammatory markers (original) (raw)
Related papers
Overexpression of miR-652-5p in new onset type 1 diabetes
Clinical Diabetology, 2018
Introduction. MicroRNAs (miRNAs) are small noncoding RNA regulating gene expression at the posttranscriptional level. miRNAs have emerged as an important regulators of central and peripheral immune tolerance, therefore study the RNA molecules in the context of type 1 diabetes (T1D) pathogenesis is an important issue. The aim of this study was to investigate miR-652-5p expression level in the new onset T1D and an impact on ADAR and MARCH5, potential target genes. Material and methods. The miR-652-5p expression was investigated in the peripheral blood mononuclear cell of newly diagnosed T1D pediatric patients (n = 28) and age-matched controls (n = 28) by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). miRNA targets were analyzed by luciferase reporter assays. Results. Expression analysis revealed upregulation of miR-652-5p in T1D group compared to non-diabetic controls (p < 0.05). Luciferase reporter assay did not indicated ADAR and MARCH5 as miR-652-5p targets. Conclusion. Our study revealed miR-652-5p as potential marker of new onset type 1 diabetes.
Decreased Serum Level of miR-146a as Sign of Chronic Inflammation in Type 2 Diabetic Patients
PLoS ONE, 2014
Background: There is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation. Aim: To determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation. Methods: We performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines.chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state. Results: The Ecuadorian non-diabetic controls appeared as overweight (BMI.25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients.
Cytokine, 2015
Objectives: The role of miR-155 in immune responses of PBMCs of type 2 diabetic (T2D) patients has not been studied. Design and methods: 20 Healthy and 20 T2D subjects were participated in the study. miR-155 expression in PBMCs of the subjects was measured using real-time PCR. The levels of secreted IL-6 and TNF-a cytokines were quantified using ELISA. Results: A downregulation of miR-155 expression was observed in untreated and LPS treated PBMCs of diabetic patients compared to controls. There was a significant upregulation of miR-155 after LPS treatment in PBMCs of both control and diabetic groups. In healthy subjects and in both untreated and LPS-treated conditions, miR-155 expression was negatively correlated with weight, waist circumference and body mass index. In diabetic group, there was a negative correlation between miR-155 expression and glucose levels only in LPS treated cells. Furthermore, systolic blood pressure was found to negatively correlate with miR-155 expression in untreated PBMCs of both healthy and diabetic subjects. The results also showed a significant correlation between miR-155 expression and TNF-a and IL-6 levels in LPS treated cells. Conclusions: Our data demonstrate that miR-155 expression is reduced in PBMCs of diabetic patients and this reduced expression does not seem to be involved in increased cytokine production from PBMCs of these patients.
Immunobiology, 2013
Introduction: It is well established that type 1 diabetes (T1D) is an autoimmune disease. Controversial data exists regarding the differential control of the immune system in T1D patients compared to unaffected individuals. MicroRNAs (miRNAs) are involved in the control of gene expression (by negative regulation of gene expression at post-transcriptional level, by mediating translational repression or degradation of the mRNA targets). Their potential role in T cell activation and autoimmunity is controversial. Aim: We investigated the expression profile of miR-21a and miR-93 in PMC samples of 20 T1D patients and 20 healthy controls by means of qPCR in different glucose concentrations (basal, 11 nM and 25 mM), and we analyzed the possible relationship of this expression pattern with autoimmunity. Results: MiR-21a was significantly underexpressed in T1D samples (media values expression 0.23 ± 0.05, p < 0.01) compared to controls (values less than 1 indicate a decrease in gene expression). When the PMCs were incubated with glucose 11 mM and 25 mM, miR-21a expression decreased in controls and increased in T1D samples (0.506 ± 0.05, p < 0.04). MiR-93 was underexpressed in T1D patients (0.331 ± 0.05, p < 0.02) compared to control samples. However, when the PBMCs were incubated with glucose, no changes were observed. No association with autoimmunity was observed. Conclusion: We demonstrated that miRNAs have a differential expression in PBMCs from T1D patients compared to controls, suggesting that these miRNAs or others could be involved in T cell regulation.
Type 2 diabetes patients exhibit subclinical inflammation but the regulatory mechanisms are poorly understood. We sought to evaluate the role of miR-146a expression along with its downstream proinflammatory signals in relation to glycemic control and insulin resistance. Study subjects (n = 20 each) comprised of clinically well characterized Type 2 diabetes patients and control non-diabetic subjects. miRNA and mRNA expression levels were probed in peripheral blood mononuclear cells (PBMC) by Real-time RT-PCR and plasma levels of TNFα and IL-6 were measured by ELISA. The miR-146a expression levels were significantly decreased in PBMCs from patients with Type 2 diabetes compared to control subjects. Among the target genes of miR-146a, TRAF-6 mRNA expression was significantly increased in patients with Type 2 diabetes while there was no significant difference in the mRNA levels of IRAK1 in the study groups. In contrast, there were significantly increased levels of NFκB expression in patients with Type 2 diabetes. There was an increased trend in the levels of TNFα and IL-6 mRNA in patients with type 2 diabetes. While SOCS-3 mRNA levels increased, plasma TNFα and IL-6 levels were also significantly higher in patients with type 2 diabetes. miR-146a expression was negatively correlated to glycated hemoglobin, insulin resistance, TRAF6, and NFκB mRNA levels and circulatory levels of TNFα and IL-6. Reduced miR-146a levels are associated with insulin resistance, poor glycemic control, and several proinflammatory cytokine genes and circulatory levels of TNFα and IL-6 in Asian Indian Type 2 diabetic patients.
Journal of Immunology Research
Aims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progression has been described but remains elusive. Objectives. To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D. Methods.We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group).Results. The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls. Several miRNAs were correlated with islet autoantibodies (IA2A, GADA, and Znt8A), age, and C-peptide levels, mainly from AbP, and recent T1D groups pointing these miRNAs as relevant to T1D pathogenesis and progression. Several...
Journal of Translational Medicine, 2021
BackgroundMicroRNA-146a-5p (miR-146a-5p) is a key regulator of inflammatory processes. Expression of miR-146a-5p is altered in target organs of diabetic complications and deficiency of miR-146a-5p has been implicated in their pathogenesis. We investigated if serum miR-146a-5p levels were independently associated with micro/macrovascular complications of type 1 diabetes (DM1).MethodsA nested case–control study from the EURODIAB PCS of 447 DM1 patients was performed. Cases (n = 294) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. Total RNA was isolated from all subjects and miR-146a-5p levels measured by qPCR. Both the endogenous controls U6 snRNA and the spike (Cel-miR-39) were used to normalize the results. Logistic regression analysis was carried out to investigate the association of miR-146a-5p with diabetes complications.ResultsMiR-146a-5p levels were significantly lower in cases [1.15 (0.32–3.34)] compared to controls [1.74 (0...
Association of MiR-146 a Expression and Type 2 Diabetes Mellitus : A Meta-Analysis
2018
1. Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran. 2. Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Biology, Tehran North Branch, Islamic Azad University, Tehran, Iran. £. Both authors contributed equally to this work .
The objective of this study was to identify circulating miRNAs affected by disease duration in newly diagnosed children with type 1 diabetes. Forty children and adolescents from The Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12 and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR and quantified for 179 human plasma miRNAs. The effect of disease duration was analyzed by mixed models for repeated measurements, adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p and hsa-miR-497-5p) were found to significantly change expression (adjusted p-value…