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鉴定和贡献炎症诱导的新型 microRNA 在系统性红斑狼疮发病机制中的作用。

Identification and Contribution of Inflammation-Induced Novel MicroRNA in the Pathogenesis of Systemic Lupus Erythematosus.

机构信息

Research Service, Veteran Administration Greater Los Angeles Healthcare System, Los Angeles, CA, United States.

Division of Rheumatology, University of California, Los Angeles, Los Angeles, CA, United States.

出版信息

Front Immunol. 2022 Apr 4;13:848149. doi: 10.3389/fimmu.2022.848149. eCollection 2022.

Abstract

Recently microRNAs (miRNAs) have been recognized as powerful regulators of many genes and pathways involved in the pathogenesis of inflammatory diseases including Systemic Lupus Erythematosus (SLE). SLE is an autoimmune disease characterized by production of various autoantibodies, inflammatory immune cells, and dysregulation of epigenetic changes. Several candidate miRNAs regulating inflammation and autoimmunity in SLE are described. In this study, we found significant increases in the expression of miR21, miR25, and miR186 in peripheral blood mononuclear cells (PBMCs) of SLE patients compared to healthy controls. However, miR146a was significantly decreased in SLE patients compared to healthy controls and was negatively correlated with plasma estradiol levels and with SLE disease activity scores (SLEDAI). We also found that protein levels of IL-12 and IL-21 were significantly increased in SLE patients as compared to healthy controls. Further, our data shows that protein levels of IL-12 were positively correlated with miR21 expression and protein levels of IL-21 positively correlated with miR25 and miR186 expression in SLE patients. In addition, we found that levels of miR21, miR25, and miR186 positively correlated with SLEDAI and miR146a was negatively correlated in SLE patients. Thus, our data shows a dynamic interplay between disease pathogenesis and miRNA expression. This study has translational potential and may identify novel therapeutic targets in patients with SLE.

摘要

最近,微小 RNA(miRNAs)已被认为是参与炎症性疾病发病机制的许多基因和途径的强大调节剂,包括系统性红斑狼疮(SLE)。SLE 是一种自身免疫性疾病,其特征是产生各种自身抗体、炎症免疫细胞和表观遗传变化失调。描述了几种调节 SLE 中炎症和自身免疫的候选 miRNAs。在这项研究中,我们发现与健康对照组相比,SLE 患者外周血单核细胞(PBMCs)中 miR21、miR25 和 miR186 的表达显着增加。然而,与健康对照组相比,SLE 患者的 miR146a 显着降低,并且与血浆雌二醇水平和 SLE 疾病活动评分(SLEDAI)呈负相关。我们还发现与健康对照组相比,SLE 患者的 IL-12 和 IL-21 蛋白水平显着增加。此外,我们的数据表明,与健康对照组相比,SLE 患者的 IL-12 蛋白水平与 miR21 表达呈正相关,而 IL-21 蛋白水平与 miR25 和 miR186 表达呈正相关。此外,我们发现 miR21、miR25 和 miR186 水平与 SLEDAI 呈正相关,而 miR146a 与 SLE 患者呈负相关。因此,我们的数据表明疾病发病机制和 miRNA 表达之间存在动态相互作用。这项研究具有转化潜力,可能为 SLE 患者确定新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb48/9013931/f193a2a8f269/fimmu-13-848149-g001.jpg

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