Although rheumatoid arthritis (RA) has long posed a major threat to global health, the mechanisms driving the development and progression of RA remain incompletely understood. In the present study, we investigated the effects of G protein-coupled receptor 43 (GPR43/FFAR2) in various aspects of the pathogenesis of RA. To our knowledge, this is the first study to demonstrate that GPR43 is expressed on human fibroblast-like synoviocytes (FLS). Furthermore, we show that GPR43 is upregulated in FLS exposed to tumor necrosis factor-α (TNF-α). Importantly, our findings demonstrate that activation of GPR43 using its specific agonist significantly suppressed expression of the following key factors of RA: cytokines, such as interleukin-6 (IL-6), IL-8, high mobility group protein 1 (HMG-1); chemokines, such as monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cellular adhesion molecule 1 (VCAM-1); markers of oxidative stress, such as production of reactive oxygen species (ROS) and 4-hydroxynoneal (4-HNE); degradative enzymes, such as matrix metalloproteinase-3 (MMP-3) and MMP-13; and activation of the nuclear factor-κB (NF-κB) inflammatory signaling pathway. These results suggest a promising potential role for GPR43 as a specific target in the treatment and prevention of RA.

中文翻译：

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GPR43 的激活抑制人成纤维细胞样滑膜细胞中 TNF-α 诱导的炎症反应。

尽管类风湿性关节炎 (RA) 长期以来一直对全球健康构成重大威胁，但驱动 RA 发展和进展的机制仍未完全了解。在本研究中，我们研究了 G 蛋白偶联受体 43 (GPR43/FFAR2) 在 RA 发病机制的各个方面的影响。据我们所知，这是第一项证明 GPR43 在人成纤维细胞样滑膜细胞 (FLS) 上表达的研究。此外，我们表明 GPR43 在暴露于肿瘤坏死因子-α（TNF-α）的 FLS 中上调。重要的是，我们的研究结果表明，使用其特异性激动剂激活 GPR43 可显着抑制以下 RA 关键因素的表达：细胞因子，如白细胞介素 6 (IL-6)、IL-8、高迁移率族蛋白 1 (HMG-1 ); 趋化因子，如单核细胞趋化蛋白 1 (MCP-1)，细胞间粘附分子 1 (ICAM-1) 和血管细胞粘附分子 1 (VCAM-1)；氧化应激的标志物，例如活性氧 (ROS) 和 4-羟基壬醛 (4-HNE) 的产生；降解酶，如基质金属蛋白酶-3 (MMP-3) 和 MMP-13；和激活核因子-κB (NF-κB) 炎症信号通路。这些结果表明 GPR43 作为治疗和预防 RA 的特定靶标具有有希望的潜在作用。