Zou Yaoyao, Zhang Xuepei, Liang Jinjian, Peng Liqin, Qin Jiale, Zhou Feng, Liu Ting, Dai Lie
Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Guangzhou, China.
Zhong Shan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Bone Joint Res. 2022 Sep;11(9):639-651. doi: 10.1302/2046-3758.119.BJR-2021-0398.R2.
To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms.
Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay.
A total of 63 RA patients and ten controls were included. Expression of MUC1 was observed in both the synovial lining and sublining layer. The percentage of MUC1+ cells in the lining layer of synovium was significantly higher in RA than that in control, and positively correlated to joint destruction scores of RA. Meanwhile, MUC1+ cells in the sublining layer were positively correlated to the Krenn subscore of inflammatory infiltration. Knockdown of MUC1, rather than GO-203 treatment, ameliorated the expression of proinflammatory cytokines, cell migration, and invasion of rheumatoid synoviocytes. Knockdown of MUC1 decreased expression of RhoA, Cdc42, and Rac1. Treatment with LPA compromised the inhibition of migration and invasion, but not inflammation, of synoviocytes by MUC1 knockdown.
Upregulated MUC1 promotes the aggression of rheumatoid synoviocytes via Rho guanosine triphosphatases (GTPases), thereby facilitating synovitis and joint destruction during the pathological process of RA.Cite this article: 2022;11(9):639-651.
探讨黏蛋白1（MUC1）在类风湿关节炎（RA）中的滑膜表达及其作用，以及可能的下游机制。
从一个RA队列中招募有合格滑膜样本的患者。获取诊断为非炎性骨科关节病患者的滑膜作为对照。通过免疫组织化学和免疫荧光评估MUC1在滑膜和成纤维样滑膜细胞中的表达和定位。采用小干扰RNA和MUC1抑制剂GO-203抑制MUC1。溶血磷脂酸（LPA）用作Rho相关途径的激活剂。使用定量实时聚合酶链反应（PCR）和Transwell小室试验评估炎性细胞因子的表达、细胞迁移和侵袭。
共纳入63例RA患者和10例对照。在滑膜衬里层和衬里下层均观察到MUC1的表达。RA患者滑膜衬里层中MUC1+细胞的百分比显著高于对照组，且与RA的关节破坏评分呈正相关。同时，衬里下层中的MUC1+细胞与炎性浸润的Krenn评分呈正相关。敲低MUC1而非GO-203处理可改善类风湿滑膜细胞中促炎细胞因子的表达、细胞迁移和侵袭。敲低MUC1可降低RhoA、Cdc42和Rac1的表达。用LPA处理可减弱MUC1敲低对滑膜细胞迁移和侵袭的抑制作用，但不影响对炎症的抑制作用。
MUC1上调通过Rho鸟苷三磷酸酶（GTPases）促进类风湿滑膜细胞的侵袭，从而在RA病理过程中促进滑膜炎和关节破坏。引用本文：2022；11(9):639-651。
