Qin Si, Wang Fengming, Zhou Meng, Ding Wen'ge, Chen Lujun, Lu Yahua
Department of General Internal Medicine, The Third Affiliated Hospital of Soochow University Changzhou 213003, Jiangsu, China.
Testing Center, Center for Disease Prevention and Control Changzhou 213000, Jiangsu, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9286-92. eCollection 2015.
Membrane-type 1 matrix metalloproteinase (MT1-MMP, also known as MMP14), the best characterized membrane-anchored MMP, is an important matrix-degrading proteinase that could digest a broad spectrum of extracellular matrix proteins and accelerate angiogenesis. We have previously reported that some MMPs involved in the angiogenesis and the pannus formation within the joint, leading to the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). In the present study, we used immunohistochemistry assay and con-focal scanning technique to study the detailed immunolocalization of MT1-MMP in human RA synovium tissues as well as the infiltrating immune cell subsets. Our results showed that the positive MT1-MMP immunostaining could be found in synoviocytes, vascular endothelial cells, infiltrating macrophages and monocytes in RA synovium tissues, while weak or negative immunostaining could be found in infiltrating T cells, B cells and NK cells, respectively. Moreover, the Ki-67(+) highly proliferating synoviocytes also showed higher MT1-MMP expression in RA synoviocytes. Thus, the aberrant expression of MT1-MMP in RA synoviocytes as well as infiltrating immune cells may contribute to the proliferation of the synoviocytes, and the angiogenesis and the pannus formation in RA pathological progression.
膜型1基质金属蛋白酶(MT1-MMP,也称为MMP14)是特征最明确的膜锚定MMP,是一种重要的基质降解蛋白酶,可消化多种细胞外基质蛋白并加速血管生成。我们之前报道过,一些MMP参与关节内血管生成和血管翳形成,在类风湿性关节炎(RA)的病理过程中导致关节软骨和骨侵蚀。在本研究中,我们使用免疫组织化学分析和共聚焦扫描技术研究MT1-MMP在人RA滑膜组织以及浸润免疫细胞亚群中的详细免疫定位。我们的结果显示,在RA滑膜组织的滑膜细胞、血管内皮细胞、浸润的巨噬细胞和单核细胞中可发现MT1-MMP免疫染色阳性,而在浸润的T细胞、B细胞和NK细胞中分别可发现弱阳性或阴性免疫染色。此外,在RA滑膜细胞中,Ki-67(+)高增殖滑膜细胞也显示出较高的MT1-MMP表达。因此,MT1-MMP在RA滑膜细胞以及浸润免疫细胞中的异常表达可能有助于滑膜细胞增殖以及RA病理进展中的血管生成和血管翳形成。