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[类风湿关节炎患者中miR-342-3p的表达及其对滑膜成纤维细胞炎症和迁移的影响]

[Expression of miR-342-3p in rheumatoid arthritis patients and its effect on synovial fibroblast inflammation and migration].

作者信息

Zhou Q, Liu J, Sun Y, Chen X, Zhang X, Ding X

机构信息

First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230012, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2022 Nov 20;42(11):1712-1719. doi: 10.12122/j.issn.1673-4254.2022.11.16.

DOI:10.12122/j.issn.1673-4254.2022.11.16
PMID:36504065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9742770/
Abstract

OBJECTIVE

To investigate the expression level of miR-342-3p in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) and its effect on inflammatory response and migration of synovial fibroblasts in RA (RA-FLS).

METHODS

PBMCs were collected from 30 healthy individuals and 50 RA patients for detecting the expression of miR-342-3p, and its correlation with the clinical indicators RF, ESR, anti-CCP, hs-CRP, C3, DAS-28, SAS, and SDS was analyzed. In RA-FLS cultures, the effect of transfection of miR-342-3p mimics and inhibitor on TNF--induced inflammatory response of the cells was evaluated by detecting the expressions of IL-1β, IL-6, IL-10, and TNF- using ELISA. CCK8 assay and Transwell assay were used for detecting the changes in cell viability and migration ability of the synovial cells.

RESULTS

In RA patients, the expression level of miR-342-3p was significantly lowered in the PBMCs ( < 0.05) with an area under the ROC curve of 97.53% and showed inverse correlations with RF (=-0.321), ESR(=-0.284), anti-CCP (=-0.355), hs-CRP (=-0.320), C3 (=-0.294), DAS-28 (=-0.395), SAS (=-0.366), and SDS (=-0.397) (all < 0.05); a low expression of miR-342-3p was strongly associated with elevated levels of anti-CCP, DAS-28, SDS, and SAS (all with a rule support greater than 85%, confidence greater than 88%, and lift greater than 1). In cultured RA-FLS, TNF- stimulation significantly increased the cell viability ( < 0.05), upregulated the expressions of IL-1β, IL-6, and TNF-, and lowered the expression of IL-10 ( < 0.05). These changes were significantly suppressed by transfection of the cells with miR-342-3p mimics ( < 0.05) but enhanced by transfection with miR-342-3p inhibitor ( < 0.05).

CONCLUSION

The expression of miR-342-3p is decreased in the PBMCs of RA patients. A lowered expression of miR-342-3p contributes to the pathogenesis of RA by promoting inflammatory responses and migration of RA-FLS.

摘要

目的

探讨类风湿关节炎(RA)患者外周血单个核细胞(PBMCs)中miR-342-3p的表达水平及其对RA患者滑膜成纤维细胞(RA-FLS)炎症反应和迁移的影响。

方法

收集30例健康个体和50例RA患者的PBMCs,检测miR-342-3p的表达,并分析其与临床指标RF、ESR、抗CCP、hs-CRP、C3、DAS-28、SAS和SDS的相关性。在RA-FLS培养物中,通过ELISA检测IL-1β、IL-6、IL-10和TNF-的表达,评估转染miR-342-3p模拟物和抑制剂对TNF-诱导的细胞炎症反应的影响。采用CCK8法和Transwell法检测滑膜细胞的活力和迁移能力变化。

结果

RA患者PBMCs中miR-342-3p表达水平显著降低(<0.05),ROC曲线下面积为97.53%,与RF(=-0.321)、ESR(=-0.284)、抗CCP(=-0.355)、hs-CRP(=-0.320)、C3(=-0.294)、DAS-28(=-0.395)、SAS(=-0.366)和SDS(=-0.397)均呈负相关(均<0.05);miR-342-3p低表达与抗CCP、DAS-28、SDS和SAS水平升高密切相关(所有规则支持率均大于85%,置信度均大于88%,提升度均大于1)。在培养的RA-FLS中,TNF-刺激显著提高细胞活力(<0.05),上调IL-1β、IL-6和TNF-的表达,降低IL-10的表达(<0.05)。用miR-342-3p模拟物转染细胞可显著抑制这些变化(<0.05),而用miR-342-3p抑制剂转染则增强这些变化(<0.05)。

结论

RA患者PBMCs中miR-342-3p表达降低。miR-342-3p表达降低通过促进RA-FLS的炎症反应和迁移,参与RA的发病机制。

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