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RBPJ 的表达及其在类风湿关节炎中的潜在作用。

The expression of RBPJ and its potential role in rheumatoid arthritis.

机构信息

Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Street of Linhai City, Linhai, 317000, China.

Key Laboratory of System Medicine and Precision Diagnosis and Treatment of Taizhou, Luqiao, China.

出版信息

BMC Genomics. 2024 Sep 30;25(1):899. doi: 10.1186/s12864-024-10804-2.

DOI:10.1186/s12864-024-10804-2
PMID:39350019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11441141/
Abstract

BACKGROUND

Recombination signal-binding protein for immunoglobulin kappa J region (RBPJ) is a transcriptional regulator that plays an important role in maintaining immune homeostasis. This study aimed to estimate the expression of RBPJ in rheumatoid arthritis (RA) patients and investigate its relationship with RA.

METHODS

A total of 83 newly diagnosed RA patients and 70 healthy controls were included. mRNA was extracted from peripheral blood mononuclear cells (PBMCs), and the expression of RBPJ was detected using quantitative real-time PCR (qRT‒PCR). An RA dataset (GSE89408) was obtained from the Gene Expression Omnibus (GEO) database, and RA synovial tissues were divided into two groups. The differentially expressed genes (DEGs) were selected with the "DESeq2" R package.

RESULTS

RBPJ expression was lower in RA patients than in health controls and was negatively correlated with the DAS28 score, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR). RA synovial tissues from GSE89408 were classified into RBPJ-low (≤ 25%) and RBPJ-high (≥ 75%) groups according to RBPJ expression, and 562 DEGs were identified. Gene Ontology (GO) enrichment analyses revealed that the DEGs significantly affected the regulation of T cell activation and lymphocyte/mononuclear cell differentiation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most enriched pathways of DEGs were the T cell receptor signaling pathway, Th1/2 and Th17 cell differentiation, the PI3K - Akt signaling pathway and cytokine‒cytokine receptor interaction. CytoHubba Plugin revealed that most of the top 10 genes were involved in osteoclast differentiation, the T cell receptor signaling pathway and cytokine‒cytokine receptor interaction.

CONCLUSIONS

RBPJ expression was significantly lower in RA patients and negatively correlated with disease activity. GEO dataset analysis demonstrated that RBPJ may be involved in osteoclast differentiation, T cell activation and differentiation, and the T cell receptor signaling pathway. Our research may contribute to understanding the potential mechanisms by which RBPJ regulates T cell differentiation and cytokine‒cytokine receptor interaction in RA patients.

摘要

背景

免疫球蛋白 κJ 区重组信号结合蛋白(RBPJ)是一种转录调节因子,在维持免疫稳态方面发挥着重要作用。本研究旨在评估 RBPJ 在类风湿关节炎(RA)患者中的表达,并探讨其与 RA 的关系。

方法

纳入 83 例新诊断的 RA 患者和 70 名健康对照者。从外周血单核细胞(PBMC)中提取 mRNA,采用实时定量 PCR(qRT-PCR)检测 RBPJ 的表达。从基因表达综合数据库(GEO)中获得 RA 数据集(GSE89408),并将 RA 滑膜组织分为两组。使用“DESeq2”R 包选择差异表达基因(DEGs)。

结果

RA 患者的 RBPJ 表达低于健康对照组,且与 DAS28 评分、C 反应蛋白(CRP)水平和红细胞沉降率(ESR)呈负相关。根据 RBPJ 表达,将 GSE89408 中的 RA 滑膜组织分为 RBPJ-低(≤25%)和 RBPJ-高(≥75%)组,鉴定出 562 个 DEGs。GO 富集分析显示,DEGs 显著影响 T 细胞激活和淋巴细胞/单核细胞分化的调节。KEGG 通路分析显示,DEGs 最富集的通路是 T 细胞受体信号通路、Th1/2 和 Th17 细胞分化、PI3K-Akt 信号通路和细胞因子-细胞因子受体相互作用。CytoHubba 插件显示,前 10 个基因中的大多数都与破骨细胞分化、T 细胞受体信号通路和细胞因子-细胞因子受体相互作用有关。

结论

RA 患者的 RBPJ 表达显著降低,且与疾病活动度呈负相关。GEO 数据集分析表明,RBPJ 可能参与破骨细胞分化、T 细胞激活和分化以及 T 细胞受体信号通路。我们的研究可能有助于理解 RBPJ 调节 RA 患者 T 细胞分化和细胞因子-细胞因子受体相互作用的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/38185414610d/12864_2024_10804_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/56bc663c49a3/12864_2024_10804_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/ccd29960a983/12864_2024_10804_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/38185414610d/12864_2024_10804_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/56bc663c49a3/12864_2024_10804_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/ea7b741e6f3f/12864_2024_10804_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/3f4ba8b3bd13/12864_2024_10804_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/f1b8be7bdd6a/12864_2024_10804_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/6572f20ecfe5/12864_2024_10804_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/fc07a852b442/12864_2024_10804_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/ccd29960a983/12864_2024_10804_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d19b/11441141/38185414610d/12864_2024_10804_Fig8_HTML.jpg

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