microRNA-143-3p contributes to inflammatory reactions by targeting FOSL2 in PBMCs from patients with autoimmune diabetes
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ORIGINAL ARTICLE
microRNA‑143‑3p contributes to inflammatory reactions by targeting FOSL2 in PBMCs from patients with autoimmune diabetes mellitus Shan Pan1,2 · Mengyu Li1,2 · Haibo Yu1,2 · Zhiguo Xie1,2 · Xia Li1,2 · Xianlan Duan1,2 · Gan Huang1,2 · Zhiguang Zhou1,2 Received: 3 January 2020 / Accepted: 5 August 2020 © Springer-Verlag Italia S.r.l., part of Springer Nature 2020
Abstract Aim Autoimmune diabetes mellitus (defined as ADM) comprises classical type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). In this study, microRNAs (miRNAs) expression profiles and functions in peripheral blood mononuclear cells (PBMCs) of ADM patients were mapped and used to explore epigenetic regulation of the pathogenesis of ADM. Methods PBMCs samples from T1DM patients, LADA patients, and type 2 diabetes mellitus (T2DM) patients, as well as age- and sex-matched healthy controls for T1DM and T2DM, respectively, were collected and were sequenced to screen the miRNAs expression profiles. The target genes were verified by dual-luciferase reporter assay. Silencing or overexpressing of the differentially expressed miRNAs, or simultaneously silencing the miRNAs and it’s target gene, and then levels of the mRNAs, protein and cytokines were detected. Results miR-143-3p expression was upregulated in ADM patients. The target gene of miR-143-3p was identified as Fosrelated antigen 2 (FOSL2). Transfection of a miR-143-3p inhibitor into PBMCs upregulated FOSL2 expression, resulting in a downregulated expression of the IL-2, TNF-α, and IFN-γ, and an upregulated expression of IL-6. Transfection of a miR-143-3p mimic into PBMCs downregulated FOSL2 expression, leading to an upregulation of IL-2 and TNF-α expression and a downregulation of IL-6 expression. When silencing FOSL2 while inhibiting miR-143-3p in PBMCs, there was no significant change in expression of the FOSL2 mRNA, protein and cytokines. Conclusion The expression of miR-143-3p in PBMCs from ADM patients is upregulated. miR-143-3p could function in the pathogenesis of ADM by modulating the inflammatory reaction through FOSL2. Keywords Autoimmune diabetes mellitus · PBMCs · miR-143-3p · FOSL2 · Cytokines
Introduction
Managed By Massimo Federici. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00592-020-01591-9) contains supplementary material, which is available to authorized users. * Gan Huang [email protected] 1
Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China
Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha 410011, Hunan, China
2
Autoimmune diabetes mellitus (defined as ADM) includes classical type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA), and is characterized by the presence of diabetes-associated autoantibodies [1, 2]. There is a high prevalence of T1DM in China
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