In situ expression of matrix-degrading enzymes in inflammatory bowel disease

基质金属蛋白酶(MMPs)是一类具有代表性的基质降解酶，参与胚胎发生、组织重塑、癌细胞侵袭转移等多种病理生理过程。炎症性肠病(IBD)是一种影响人类肠道的顽固性炎症性疾病。MMPs的组织表达被认为是组织重塑的一个因素，而不是简单地参与组织破坏的一个因素。本研究旨在探讨MMPs-1、2、8、9、TIMPS-1、TIMPS-2、MT1-MMPs和I型前胶原(PC-I)在IBD组织中的表达及意义。溃疡期MMPs-1、8、9和TIMP-1表达丰富，炎症细胞丰富。小静脉的血管平滑肌细胞/小静脉上皮细胞也表达MMP1、TIMP-1和PC-I，溃疡基底部的巨噬细胞表达MTI-MMP1。溃疡基底部炎性活动区周围形成的纤维化活动区表达MMP2、TIMP-2和PC-I。结果提示，溃疡基底部炎性活动区表达多种基质降解酶，使间质水肿(非纤维化)，血管平滑肌细胞参与了这一过程。一些基质降解酶参与了发炎过程。因此，MMPs在IBD中的基本病理生理意义被认为是组织重塑。

Matrix metalloproteinases (MMPs) are representative matrix-degrading enzymes, and they are involved in various pathophysiologic events including embryogenesis, tissue remodeling, and cancer cell invasion and metastasis. Inflammatory boweldisease (IBD) is a intractable inflammatory disease affecting human bowel. Tissue expression of MMiPs is now regarded as a factor of tissue remodeling rather than a factor simply involved in the tissue destruction. The present study focused on the tissue expression of MMPs-1, 2, 8, and 9, TIMPs-1 and 2, MT1-MMP and type Iprocollagen (PC-I) to reveal their significance in IBD.In ulcer hases, MMPs-1, 8and 9 and TIMP- 1 were abundantly expressed, where inflammatory cells were abundant. Vascular smooth muscle cells/p ericytes of venules were also positive for MMP- 1, TIMP- 1 and PC-I.MTI-MMP were positive in macrophages in ulcer bases. Areas with active fibrosis which were formed surrounding the active inflammatory areas in ulcer bases expressed MMP-2, TIMP-2 and PC-I.Our results suggest that in active inflammatory area in ulcer bases expressed various matrix degrading enzymes to make the stroma edematous (not fibrotic), and that vascular smooth muscle cells are involved in this process. Some of matrix-degrading enzymes are involved in firosis process. Therefore, the basic pathophysiologic significance of MMPs in IBD is considered to be tissue remodeling.