Activating transcription factor 2(ATF2), a transcription factor belonging to the AP-1 family, plays an important role in inflammation. However, its biological functions and underlying molecular mechanisms in rheumatoid arthritis (RA) remain unclear. Western blot and immunohistochemistry were used to identify the expression of ATF2 and Sprouty2(SPRY2) in RA synovial tissues. SW982 cells were stimulated by TNF-α to establish an in vitro RA fibroblast-like synoviocyte (RA-FLS) model. Transwell and monolayer wound-healing were used to detect cell migration and invasion. RNA interference (si-ATF2) and adenovirus vector (Ad-SPRY2) methods were employed to manipulate ATF2 or SPRY2 expression in SW982 cells. The protein expression and phosphorylation levels in SW982 cells were evaluated by western blot. ATF2 expression and phosphorylation were upregulated in the RA synovial tissues. In RA-FLS model, ATF2 expression and phosphorylation were increased in a time-dependent manner. ATF2 knockdown inhibited the migration and invasion of RA-FLS model, reducing the inflammatory factors, which was consistent with the influence on cell behaviors caused by SPRY2 overexpression. Moreover, SPRY2 overexpression inhibited the TNF-α-induced phosphorylation of ERK and ATF2 in SW982 cells. The high expression and phosphorylation of ATF2 promoted migration and invasion of RA-FLSs. SPRY2 might inhibited the inflammatory responses of RA-FLSs via suppressing ERK-ATF2 pathway.

激活转录因子 2 (ATF2) 是一种属于 AP-1 家族的转录因子，在炎症中起重要作用。然而，其在类风湿性关节炎 (RA) 中的生物学功能和潜在分子机制仍不清楚。Western印迹和免疫组织化学用于鉴定RA滑膜组织中ATF2和Sprouty2（SPRY2）的表达。TNF-α 刺激 SW982 细胞建立体外RA 成纤维细胞样滑膜细胞 (RA-FLS) 模型。Transwell 和单层伤口愈合用于检测细胞迁移和侵袭。RNA 干扰 (si-ATF2) 和腺病毒载体 (Ad-SPRY2) 方法被用来操纵 SW982 细胞中的 ATF2 或 SPRY2 表达。通过蛋白质印迹评估 SW982 细胞中的蛋白质表达和磷酸化水平。ATF2 表达和磷酸化在 RA 滑膜组织中上调。在 RA-FLS 模型中，ATF2 表达和磷酸化呈时间依赖性增加。ATF2敲低抑制RA-FLS模型的迁移和侵袭，减少炎症因子，这与SPRY2过表达对细胞行为的影响一致。此外，SPRY2 过表达抑制了 TNF-α 诱导的 SW982 细胞中 ERK 和 ATF2 的磷酸化。ATF2的高表达和磷酸化促进了RA-FLSs的迁移和侵袭。SPRY2 可能抑制 RA-FLSs 的炎症反应通过抑制 ERK-ATF2 通路。