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针刺治疗类风湿关节炎的疗效与着丝粒蛋白 F 表达相关。

Therapeutic effects of acupuncture in rheumatoid arthritis are associated with centromere protein F expression.

机构信息

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

Department of Acupuncture and Tuina, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China.

出版信息

Allergol Immunopathol (Madr). 2022 May 1;50(3):47-54. doi: 10.15586/aei.v50i3.564. eCollection 2022.

Abstract

OBJECTIVE

The objective of this study is to study the critical role of CENPF in regulation of rheumatoid arthritis with acupuncture treatment.

METHODS

PCA was used to analyze the different expression genes between AP treatment group and control group. Volcano plot and random forest model were used to analyze the decreased and increased expression genes. RT-qPCR and IF were used to measure the expression of CENPF in CIA model rat with or without AP treatment. The expression of MCP-1, TNF-α and IL-6 was measured by western blotting. The pathology character and arthritis index were used to analyze the severity of joint injury.

RESULTS

PCA data showed that the expression of genes was different between AP treatment group and control group from GEO datasets. Volcano plot and random forest model analysis indicated that CENPF is the most significantly increased expression gene after AP treatment. RT-qPCR and IF assay showed that CENPF is reduced expression in CIA model rat, while CENPF is upregulated expression in CIA model rat with AP treatment. Furthermore, overexpression of CENPF reduced the increasing of MCP-1, TNF-α and IL-6 in CIA model rat. On the contrary, CENPF deficiency induced the expression of MCP-1, TNF-α and IL-6 in CIA model rat. Additionally, the expression of MCP-1, TNF-α and IL-6 in CIA model rat was suppressed, whereas knockdown of CENPF antagonized the decrease of MCP-1, TNF-α and IL-6 in CIA model rat with AP treatment.

CONCLUSIONS

CENPF may be a key gene in regulation of the therapeutic effects of acupuncture in rheumatoid arthritis. Rheumatoid arthritis is a globally common autoimmune inflammatory disease found especially in China. Acupuncture (AP), a traditional Chinese medicine (TCM) treatment method, is commonly used for treating rheumatoid arthritis. Many studies have demonstrated that acupuncture alone or in combination with other treatments is beneficial to treat clinical situation of rheumatoid arthritis, thus improving function and quality of life. In this study, we found that centromere protein F (CENPF) is a key gene in rheumatoid arthritis with acupuncture treatment by using differentially expressed genes (DEGs) and random forest model analysis of GSE57983 and GSE77298. Acupuncture helps to up-regulate the expression of CENPF in tissues in rheumatoid arthritis. Functionally, overexpression of CENPF inhibits monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and Interleukin (IL)-6 expressions whereas deficiency of CENPF facilitates MCP-1, TNF-α, and IL-6 expressions in a collagen-induced arthritis (CIA) rat model. Furthermore, knocked down CENPF with acupuncture treatment antagonizes the inhibition of MCP-1, TNF-α, and IL-6 expressions in a CIA rat model. CENPF could be a crucial biomarker in regulating function of acupuncture in treating rheumatoid arthritis.

摘要

目的

本研究旨在探讨中心体蛋白 F(CENPF)在针灸治疗类风湿关节炎中的关键作用。

方法

采用 PCA 分析 AP 治疗组和对照组之间差异表达的基因。火山图和随机森林模型分析用于分析下调和上调的表达基因。采用 RT-qPCR 和 IF 检测 CIA 模型大鼠经 AP 治疗后 CENPF 的表达。采用 Western blot 检测单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达。通过病理特征和关节炎指数分析关节损伤的严重程度。

结果

PCA 数据显示,来自 GEO 数据集的 AP 治疗组和对照组之间的基因表达存在差异。火山图和随机森林模型分析表明,CENPF 是 AP 治疗后表达增加最显著的基因。RT-qPCR 和 IF 检测显示,CENPF 在 CIA 模型大鼠中表达下调,而 CENPF 在 CIA 模型大鼠经 AP 治疗后表达上调。此外,CENPF 的过表达降低了 CIA 模型大鼠中 MCP-1、TNF-α 和 IL-6 的增加。相反,CENPF 缺乏诱导 CIA 模型大鼠中 MCP-1、TNF-α 和 IL-6 的表达。此外,CENPF 敲低抑制了 CIA 模型大鼠中 MCP-1、TNF-α 和 IL-6 的表达,而 CENPF 敲低拮抗了 CIA 模型大鼠经 AP 治疗后 MCP-1、TNF-α 和 IL-6 的表达降低。

结论

CENPF 可能是针灸治疗类风湿关节炎疗效的关键基因。类风湿关节炎是一种常见的全球性自身免疫性炎症性疾病,在中国尤为常见。针灸(AP)是一种传统的中药(TCM)治疗方法,常用于治疗类风湿关节炎。许多研究表明,针灸单独或与其他治疗方法联合使用对治疗类风湿关节炎的临床情况有益,从而改善功能和生活质量。在这项研究中,我们通过 GSE57983 和 GSE77298 的差异表达基因(DEGs)和随机森林模型分析发现,中心体蛋白 F(CENPF)是针灸治疗类风湿关节炎的关键基因。针灸有助于上调类风湿关节炎组织中 CENPF 的表达。功能上,CENPF 的过表达抑制单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子(TNF)-α 和白细胞介素(IL)-6 的表达,而 CENPF 的缺乏促进 MCP-1、TNF-α 和 IL-6 在胶原诱导性关节炎(CIA)大鼠模型中的表达。此外,CENPF 敲低与针灸治疗联合拮抗 CIA 大鼠模型中 MCP-1、TNF-α 和 IL-6 的抑制作用。CENPF 可能是调节针灸治疗类风湿关节炎功能的关键生物标志物。

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