Department of Orthopedics, The first Affiliated Hospital of Soochow University, Suzhou, China.
IUBMB Life. 2019 Jul;71(7):969-977. doi: 10.1002/iub.2031. Epub 2019 Mar 21.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of unknown etiology characterized by degradation of cartilage and bone, accompanied by unimpeded proliferation of synoviocytes of altered phenotype. In the present study, we investigated the involvement of the glucagon-like peptide 1 (GLP-1) receptor on human fibroblast-like synoviocytes (FLS) in the pathogenesis of RA using the selective GLP-1 agonist exenatide, a licensed drug used for the treatment of type 2 diabetes. Our results indicate that exenatide may play a role in regulating tumor necrosis factor-α-induced mitochondrial dysfunction by increasing mitochondrial membrane potential, oxidative stress by reducing the production of reactive oxygen species, the expression of NADPH oxidase 4, expression of matrix metalloproteinase (MMP)-3 and MMP-13, release of proinflammatory cytokines including interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1, and high-mobility group protein 1, as well as activation of the p38/nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α/nuclear factor κB signaling pathway in primary human RA FLS. These positive results indicate that exenatide may have potential as a therapeutic agent for the treatment and prevention of RA. © 2019 IUBMB Life, 9999(9999):1-9, 2019.
类风湿关节炎（RA）是一种病因不明的慢性炎症性自身免疫性疾病，其特征为软骨和骨降解，伴有表型改变的滑膜细胞不受阻碍地增殖。在本研究中，我们使用选择性 GLP-1 激动剂 exenatide（一种用于治疗 2 型糖尿病的已上市药物）研究了 GLP-1 受体在人成纤维样滑膜细胞（FLS）中的参与 RA 的发病机制。我们的结果表明，exenatide 可能通过增加线粒体膜电位，减少活性氧产生来调节肿瘤坏死因子-α诱导的线粒体功能障碍，NADPH 氧化酶 4 的表达，基质金属蛋白酶（MMP）-3 和 MMP-13 的表达，包括白细胞介素-1β（IL-1β），IL-6，单核细胞趋化蛋白-1 和高迁移率族蛋白 1 在内的促炎细胞因子的释放，以及 p38/核因子κ轻链增强子 B 细胞抑制剂，α/核因子κB 信号通路的激活。这些阳性结果表明，exenatide 可能具有作为治疗和预防 RA 的治疗剂的潜力。©2019 IUBMB Life，9999（9999）：1-9，2019。
