Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2279, USA.
Cancer Res. 2010 Jan 1;70(1):30-5. doi: 10.1158/0008-5472.CAN-09-2899.
Helicobacter pylori-induced gastritis is the strongest singular risk factor for gastric adenocarcinoma. Matrix metalloproteinase-7 (MMP-7) is a proteolytic enzyme that can modify the intestinal microbial replicative niche as well as affect tumorigenesis, and H. pylori stimulates expression of MMP-7 in gastric epithelial cells in vitro. Utilizing a transgenic murine model of H. pylori-mediated injury, our experiments now show that gastric inflammation is increased within the context of MMP-7 deficiency, which involves both Th1- and Th17-mediated pathways. Enhanced gastritis in H. pylori-infected mmp-7-/- mice is strongly linked to accelerated epithelial cellular turnover. However, more severe inflammation and heightened proliferation and apoptosis are not dependent on MMP-7-mediated bacterial eradication. Collectively, these studies indicate that H. pylori-mediated induction of MMP-7 may serve to protect the gastric mucosa from pathophysiologic processes that promote carcinogenesis.
幽门螺杆菌引起的胃炎是导致胃腺癌的最强单一风险因素。基质金属蛋白酶-7（MMP-7）是一种蛋白水解酶，可改变肠道微生物的复制生态位，并影响肿瘤发生，而幽门螺杆菌可在体外刺激胃上皮细胞中 MMP-7 的表达。利用幽门螺杆菌介导损伤的转基因小鼠模型，我们的实验现在表明，在 MMP-7 缺乏的情况下，胃炎症会增加，这涉及 Th1 和 Th17 介导的途径。在感染幽门螺杆菌的 mmp-7-/-小鼠中，增强的胃炎与上皮细胞更替的加速密切相关。然而，更严重的炎症、更高的增殖和凋亡并不依赖于 MMP-7 介导的细菌清除。总的来说，这些研究表明，幽门螺杆菌诱导的 MMP-7 可能有助于保护胃黏膜免受促进癌变的病理生理过程的影响。
