Volin Michael V, Shahrara Shiva, Haines G Kenneth, Woods James M, Koch Alisa E
Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois 60515, USA.
Arthritis Rheum. 2008 Jan;58(1):46-52. doi: 10.1002/art.23174.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hypertrophy of the synovial tissue, leukocyte infiltration, angiogenesis, and ultimately joint destruction. Mucins (MUCs) are a family of heavily glycosylated proteins that protect epithelial membranes and are used as ligands for cell adhesion. MUC gene expression has been found to be altered in many cancers and inflammatory states. This study was undertaken to examine its expression in synovial tissue (ST) and role in arthritis.
We performed immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction to determine expression patterns of MUC1, MUC2, MUC3, and MUC5AC in RA, osteoarthritic (OA), and normal human ST.
MUC3 was expressed in synovial lining cells, macrophages, and fibroblasts. Significantly more RA (n=12) and OA (n=13) synovial lining cells expressed MUC3 than did normal synovial lining cells (n=7) (22% and 24% versus 0.4%, respectively; P<0.05). Additionally, macrophages in RA and OA ST expressed significantly more MUC3 than did macrophages in normal ST (50% and 51% versus 10%, respectively; P<0.05). MUC5AC was expressed at low levels in synovial lining cells, macrophages, and endothelial cells in RA and OA ST, and was barely expressed in normal ST. MUC1 and MUC2 proteins were not detected in ST. Messenger RNA (mRNA) for MUC3 and MUC5AC was detected in ST, and mRNA for MUC3 was detected in cultured ST fibroblasts.
These data demonstrate up-regulated MUC expression by ST cells and suggest a novel role of MUC3 and MUC5AC in the pathogenesis of arthritis.
类风湿关节炎(RA)是一种慢性炎症性疾病,其特征为滑膜组织肥大、白细胞浸润、血管生成,并最终导致关节破坏。黏蛋白(MUCs)是一类高度糖基化的蛋白质家族,可保护上皮膜,并用作细胞黏附的配体。已发现MUC基因表达在许多癌症和炎症状态下会发生改变。本研究旨在检测其在滑膜组织(ST)中的表达及其在关节炎中的作用。
我们进行了免疫组织化学、蛋白质印迹法及逆转录聚合酶链反应,以确定MUC1、MUC2、MUC3和MUC5AC在RA、骨关节炎(OA)及正常人ST中的表达模式。
MUC3在滑膜衬里细胞、巨噬细胞和成纤维细胞中表达。与正常滑膜衬里细胞(n = 7)相比,表达MUC3的RA(n = 12)和OA(n = 13)滑膜衬里细胞明显更多(分别为22%和24%,而正常为0.4%;P < 0.05)。此外,RA和OA ST中的巨噬细胞表达MUC3明显多于正常ST中的巨噬细胞(分别为50%和51%,而正常为10%;P < 0.05)。MUC5AC在RA和OA ST的滑膜衬里细胞、巨噬细胞和内皮细胞中低水平表达,在正常ST中几乎不表达。在ST中未检测到MUC1和MUC2蛋白。在ST中检测到MUC3和MUC5AC的信使核糖核酸(mRNA),在培养的ST成纤维细胞中检测到MUC3的mRNA。
这些数据表明ST细胞上调了MUC表达,并提示MUC3和MUC5AC在关节炎发病机制中具有新作用。