Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia.
Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia.
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DOI：
10.1038/labinvest.2012.141
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发表时间：
2012-12
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影响因子：
--
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炎症性肠病，如溃疡性结肠炎，代表了严重的健康负担，既因为组织破坏性疾病本身，也因为结肠癌的风险增加。在结肠炎中发生的基质金属蛋白酶（MMP）家族的酶的许多成员的表达增加长期以来与疾病的破坏性性质相关。然而，最近在癌症和其他MMP相关疾病中的发现使我们质疑MMP是否确实对结肠炎有害。在这里，我们专注于一个单一的MMP家族成员，MMP 10，并评估其在小鼠模型中的作用，葡聚糖硫酸钠（DSS）治疗诱导的结肠组织损伤。使用MMP10基因缺陷的小鼠，我们发现缺乏这种酶会导致疾病评分显着恶化，即使在延长的恢复期后也无法解决炎症。我们表明，MMP 10主要是由浸润骨髓细胞在小鼠和人类结肠炎。通过骨髓移植实验，我们证实骨髓来源的MMP 10有助于结肠炎的严重程度。在两轮DSS暴露后，缺乏MMP 10的小鼠在结肠中具有显著更高的发育异常病变的倾向。因此，我们得出结论，MMP 10是解决DSS诱导的结肠损伤所必需的，如果没有MMP 10，则会发生慢性炎症和最终的异型增生。
Inflammatory bowel diseases such as ulcerative colitis represent serious health burdens, both because of the tissue-damaging disease itself, and because of an elevated risk of colon cancer. The increased expression of many members of the matrix metalloproteinase (MMP) family of enzymes that occurs in colitis, has long been associated with the destructive nature of the disease. Recent findings in cancer and other MMP-associated diseases, however, led us to question whether MMPs are indeed detrimental in the setting of colitis. Here, we focus on a single MMP family member, MMP10, and assess its role in a murine model of colonic tissue damage induced by dextran sulphate sodium (DSS) treatment. Using mice genetically deficient for MMP10, we find that absence of this enzyme leads to significantly worse disease scores and failure to resolve inflammation even after extended recovery periods. We show that MMP10 is produced predominantly by infiltrating myeloid cells in both murine and human colitis. Through bone marrow transplant experiments, we confirm that bone marrow-derived MMP10 contributes to colitis severity. Mice lacking MMP10 have a significantly higher propensity for development of dysplastic lesions in the colon after two rounds of DSS exposure. Thus, we conclude that MMP10 is required for resolution of DSS-induced colonic damage, and in its absence, chronic inflammation and ultimately dysplasia occurs.
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影响因子：
30.5
作者：
Corry, DB;Rishi, K;Kheradmand, F
通讯作者：
Kheradmand, F
DOI：
10.1073/pnas.0405979102
发表时间：
2005-01-04
影响因子：
11.1
作者：
Pull, SL;Doherty, JM;Stappenbeck, TS
通讯作者：
Stappenbeck, TS
影响因子：
3.7
作者：
Laroui H;Ingersoll SA;Liu HC;Baker MT;Ayyadurai S;Charania MA;Laroui F;Yan Y;Sitaraman SV;Merlin D
通讯作者：
Merlin D
影响因子：
3.1
作者：
Medina, Carlos;Santana, Alfredo;Quintero, Enrique
通讯作者：
Quintero, Enrique
影响因子：
6.3
作者：
Matsuno, K;Adachi, Y;Imai, K
通讯作者：
Imai, K