FNDC4 通过抑制 CCL2/ERK 信号通路减少类风湿性滑膜细胞的炎症、增殖、侵袭和迁移。
FNDC4 reduces inflammation, proliferation, invasion and migration of rheumatoid synovial cells by inhibiting CCL2/ERK signaling.
机构信息
Nephrology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410000, Hunan, P.R. China.
Nephrology Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410000, Hunan, P.R. China.
出版信息
Tissue Cell. 2024 Feb;86:102294. doi: 10.1016/j.tice.2023.102294. Epub 2023 Dec 23.
BACKGROUND
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation. Fibronectin type III domain-containing protein 4 (FNDC4) is a secretory factor that can regulate inflammatory diseases. However, the role of FNDC4 in RA has not been reported so far.
METHODS
The expression of FNDC4 in synovial tissues of RA was analyzed by GEO database (GSE55235 dataset). Then, the expression of FNDC4 in RA fibroblast-like synoviocytes (RA-FLSs) was detected by RT-qPCR and western blot. After constructing FNDC4 overexpression plasmid, cell proliferation and apoptosis were detected. Wound healing and transwell assays were used to detect cell migration and invasion. Then we examined the expression of cytokines related to cell inflammation. Subsequently, the regulatory mechanism of FNDC4 was further discussed. We detected the expression of CCL2 and ERK signaling pathway related proteins downstream of FNDC4. Finally, the mechanism was discussed through the overexpression of FNDC4 and CCL2 and the addition of ERK pathway activator tBHQ.
RESULTS
GEO database showed that FNDC4 expression decreased in synovial tissues of RA. FNDC4 expression was also decreased in RA-FLSs. Overexpression of FNDC4 inhibited the proliferation, invasion and migration of RA-FLSs whereas promoted the cellapoptosis. Overexpression of FNDC4 inhibited the release of inflammatory factors in RA-FLSs. The regulatory effect of FNDC4 is achieved by inhibiting the CCL2/ERK signaling pathway.
CONCLUSION
FNDC4 reduces inflammation, proliferation, invasion and migration of RA-FLSs in RA by inhibiting CCL2/ERK signaling.
背景
类风湿关节炎（RA）是一种以慢性关节炎症为特征的自身免疫性疾病。纤维连接蛋白 III 型结构域蛋白 4（FNDC4）是一种可调节炎症性疾病的分泌因子。然而，FNDC4 在 RA 中的作用尚未有报道。
方法
通过 GEO 数据库（GSE55235 数据集）分析 RA 滑膜组织中 FNDC4 的表达。然后，通过 RT-qPCR 和 Western blot 检测 RA 成纤维样滑膜细胞（RA-FLS）中 FNDC4 的表达。构建 FNDC4 过表达质粒后，检测细胞增殖和凋亡。通过划痕愈合和 Transwell 实验检测细胞迁移和侵袭。然后检测与细胞炎症相关的细胞因子表达。随后，进一步探讨 FNDC4 的调控机制。检测 FNDC4 下游的 CCL2 和 ERK 信号通路相关蛋白的表达。最后，通过 FNDC4 和 CCL2 的过表达以及 ERK 通路激活剂 tBHQ 的添加来探讨机制。
结果
GEO 数据库显示 FNDC4 在 RA 滑膜组织中的表达降低。FNDC4 在 RA-FLS 中的表达也降低。FNDC4 的过表达抑制了 RA-FLS 的增殖、侵袭和迁移，而促进了细胞凋亡。FNDC4 的过表达抑制了 RA-FLS 中炎症因子的释放。FNDC4 的调节作用是通过抑制 CCL2/ERK 信号通路实现的。
结论
FNDC4 通过抑制 CCL2/ERK 信号通路，减少 RA-FLS 中的炎症、增殖、侵袭和迁移。
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