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

炎症性肠病基质降解酶的原位表达

• 批准号: 09670174
• 负责人: OHTANI Haruo
• 金额: $ 1.09万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670174/
• 关键词: Inflammatory bowel disease; matrix degradation; MMP-1; MT1-MMP; マトリックスメタロプロティナーゼ; 組織再構築; 免疫組織化学; in situ ハイブリダイゼーション

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.

基质金属蛋白酶（Matrix metalloproteinases，MMPs）是一种典型的基质降解酶，参与胚胎发生、组织重塑、肿瘤细胞侵袭和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难治性炎症性疾病。MMiPs的组织表达现在被认为是组织重建的因素，而不是简单地参与组织破坏的因素。本研究通过观察MMPs-1、2、8、9、TIMPs-1、2、MT 1-MMP和I型前胶原（PC-I）在IBD组织中的表达，探讨其在IBD中的意义。微静脉血管平滑肌细胞/巨噬细胞MMP- 1、TIMP- 1和PC-Ⅰ阳性，溃疡基底部巨噬细胞MTI-MMP阳性。溃疡基底部活动性炎症区周围形成的活动性纤维化区域表达MMP-2、TIMP-2和PC-1。我们的结果表明，在溃疡基底部活动性炎症区表达各种基质降解酶，使基质水肿（而不是纤维化），并且血管平滑肌细胞参与了这一过程。一些基质降解酶参与了烧伤的发生过程。因此，MMPs在IBD中的基本病理生理意义被认为是组织重塑。

项目成果

Ohnoら: "Eosinophils as a saurce of matrix metalloproteinase-9 in asthmatic airway inflammation" Am.J.Res.Cell.Mol.Biol.16. 212-219 (1997)

Ohno 等人：“嗜酸性粒细胞作为哮喘气道炎症中基质金属蛋白酶 9 的来源”Am.J.Res.Cell.Mol.Biol.16 (1997)。

Ohtani H.: "Stromal reaction in cancer tissue : Pathophysiologic significance of expression of matrix-degrading enzymes in relation to matrix turnover and immune/inflammatory reactions." Pathol Int. 48. 1-9 (1998)

Ohtani H.：“癌组织中的基质反应：基质降解酶表达与基质周转和免疫/炎症反应相关的病理生理学意义。”

Akahaneら: "Stromal expression of urokinase-type plasminugen activator receptor (UPAR) is associated with invosive growth" Liver. 18. 414-419 (1998)

Akahane 等人：“尿激酶型纤溶酶原激活剂受体 (UPAR) 的基质表达与侵入性生长相关”肝脏。 18. 414-419 (1998)