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E2F2 stimulates CCR4 expression and activates synovial fibroblast-like cells in rheumatoid arthritis
Central European Journal of Immunology ( IF 1.3 ) Pub Date : 2021-04-18 , DOI: 10.5114/ceji.2021.105243 Wanju Xu 1 , Shufeng Li 2 , Xiaotian Chang 1, 3
Central European Journal of Immunology ( IF 1.3 ) Pub Date : 2021-04-18 , DOI: 10.5114/ceji.2021.105243 Wanju Xu 1 , Shufeng Li 2 , Xiaotian Chang 1, 3
Affiliation
Introduction
E2F transcription factor 2 (E2F2) has increased expression in synovial tissues of rheumatoid arthritis (RA) and stimulates interleukin (IL)-1 and IL- production in cultured RA synovial fibroblast-like cells (RASF), which supports the importance of E2F2 in RA pathogenesis. This study investigated the effect and mechanism of E2F2 in RA.
Material and methods
Cultured RASF were transfected with anti-E2F2 siRNA, and the expression profile was analyzed with an inflammatory response and autoimmunity PCR array loaded with 84-relative genes to explore the pathogenic pathway of E2F2. Apoptosis, migration and tube-like structure formation in the RASF with transfection of anti-E2F2 siRNA or E2F2-expressing plasmids were examined using flow cytometry, transwell assays and Matrigel assays, respectively.
Results
Significantly decreased expression of chemokine receptor 4 (CCR4) was detected in RASF with inhibited E2F2 expression, and the CCR4 expression was increased in RASF with transfection of E2F2-expressing plasmids. Silencing E2F2 expression stimulated apoptosis, but retarded migration and tube-like structure formation in RASF. The opposite observation was obtained in RASF with E2F2 overexpression.
Conclusions
High E2F2 expression decreases apoptosis and increases migration and tube-like structure ability in RASF and might perform this role by up-regulating CCR4 expression, which ultimately contributes to the disease progression of RA synovial tissues.
中文翻译：
E2F2 刺激 CCR4 表达并激活类风湿性关节炎中的滑膜成纤维细胞样细胞
简介
E2F 转录因子 2 (E2F2) 在类风湿性关节炎 (RA) 滑膜组织中的表达增加，并刺激培养的 RA 滑膜成纤维细胞样细胞 (RASF) 中的白细胞介素 (IL)-1 和 IL- 产生，这支持了对类风湿性关节炎 (RA) 滑膜组织的重要性。 E2F2 在 RA 发病机制中的作用。本研究调查了 E2F2 在 RA 中的作用和机制。
材料与方法
用抗E2F2 siRNA转染培养的RASF，并用加载84个相关基因的炎症反应和自身免疫PCR阵列分析表达谱，以探索E2F2的致病途径。分别使用流式细胞术、transwell 分析和 Matrigel 分析检测了转染抗 E2F2 siRNA 或 E2F2 表达质粒的 RASF 中的细胞凋亡、迁移和管状结构形成。
结果
在 E2F2 表达受到抑制的 RASF 中检测到趋化因子受体 4 (CCR4) 的表达显着降低，而在转染 E2F2 表达质粒的 RASF 中 CCR4 表达增加。沉默 E2F2 表达会刺激细胞凋亡，但会延缓 RASF 中的迁移和管状结构形成。在 E2F2 过表达的 RASF 中获得了相反的观察结果。
结论
E2F2 高表达可减少 RASF 细胞凋亡并增加迁移和管状结构能力，并可能通过上调 CCR4 表达发挥这一作用，最终促进 RA 滑膜组织的疾病进展。
更新日期：2021-04-18
E2F transcription factor 2 (E2F2) has increased expression in synovial tissues of rheumatoid arthritis (RA) and stimulates interleukin (IL)-1 and IL- production in cultured RA synovial fibroblast-like cells (RASF), which supports the importance of E2F2 in RA pathogenesis. This study investigated the effect and mechanism of E2F2 in RA.
Material and methods
Cultured RASF were transfected with anti-E2F2 siRNA, and the expression profile was analyzed with an inflammatory response and autoimmunity PCR array loaded with 84-relative genes to explore the pathogenic pathway of E2F2. Apoptosis, migration and tube-like structure formation in the RASF with transfection of anti-E2F2 siRNA or E2F2-expressing plasmids were examined using flow cytometry, transwell assays and Matrigel assays, respectively.
Results
Significantly decreased expression of chemokine receptor 4 (CCR4) was detected in RASF with inhibited E2F2 expression, and the CCR4 expression was increased in RASF with transfection of E2F2-expressing plasmids. Silencing E2F2 expression stimulated apoptosis, but retarded migration and tube-like structure formation in RASF. The opposite observation was obtained in RASF with E2F2 overexpression.
Conclusions
High E2F2 expression decreases apoptosis and increases migration and tube-like structure ability in RASF and might perform this role by up-regulating CCR4 expression, which ultimately contributes to the disease progression of RA synovial tissues.
中文翻译：
E2F2 刺激 CCR4 表达并激活类风湿性关节炎中的滑膜成纤维细胞样细胞
简介
E2F 转录因子 2 (E2F2) 在类风湿性关节炎 (RA) 滑膜组织中的表达增加，并刺激培养的 RA 滑膜成纤维细胞样细胞 (RASF) 中的白细胞介素 (IL)-1 和 IL- 产生，这支持了对类风湿性关节炎 (RA) 滑膜组织的重要性。 E2F2 在 RA 发病机制中的作用。本研究调查了 E2F2 在 RA 中的作用和机制。
材料与方法
用抗E2F2 siRNA转染培养的RASF，并用加载84个相关基因的炎症反应和自身免疫PCR阵列分析表达谱，以探索E2F2的致病途径。分别使用流式细胞术、transwell 分析和 Matrigel 分析检测了转染抗 E2F2 siRNA 或 E2F2 表达质粒的 RASF 中的细胞凋亡、迁移和管状结构形成。
结果
在 E2F2 表达受到抑制的 RASF 中检测到趋化因子受体 4 (CCR4) 的表达显着降低，而在转染 E2F2 表达质粒的 RASF 中 CCR4 表达增加。沉默 E2F2 表达会刺激细胞凋亡，但会延缓 RASF 中的迁移和管状结构形成。在 E2F2 过表达的 RASF 中获得了相反的观察结果。
结论
E2F2 高表达可减少 RASF 细胞凋亡并增加迁移和管状结构能力，并可能通过上调 CCR4 表达发挥这一作用，最终促进 RA 滑膜组织的疾病进展。
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