Degradation of the Extracellular Matrix Components by Bacterial-derived Metalloproteases: Implications for Inflammatory Bowel Diseases
Degradation of the Extracellular Matrix Components by Bacterial-derived Metalloproteases: Implications for Inflammatory Bowel Diseases
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DOI：
10.1002/ibd.21475
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发表时间：
2011-05-01
影响因子：
4.9
通讯作者：
Shanahan, Fergus
中科院分区：
文献类型：
--
作者：
Pruteanu, Mihaela;Hyland, Niall P.;Shanahan, Fergus
背景：细胞外基质的蛋白降解是粘膜动态平衡和组织更新的一个特征，也是肠道炎症并发症的原因之一。这种蛋白分解活性是完全由宿主产生的，还是部分由肠道微生物区系产生的，尚不清楚。方法：我们从20名健康对照组、23名溃疡性结肠炎患者和18名克罗恩病(CD)患者的粪便样本中筛选细菌菌落以检测明胶溶解活性。用常规或实时聚合酶链式反应(PCR)检测金属蛋白水解酶基因。结果：在约四分之一的样本中发现明胶蛋白分解活性，无论是否存在炎症，也没有任何提高基于培养的筛查的灵敏度的尝试。这与细菌的多样性有关，尤其是在Cd中，但主要与产气荚膜梭菌有关。产气荚膜梭菌的培养上清液可降解明胶、偶氮化合物、I型胶原和基底膜IV型胶原，但不同菌株的蛋白分解活性程度不同。结果通过检测粪便DNA中的产气荚膜梭菌可乐基因(编码胶原酶)得到证实，同样无论是否有炎症。然而，在大鼠远端结肠暴露于Ussing小室产气荚膜弧菌培养上清液后，微生物来源的蛋白分解活性的生物学意义和潜在意义被证实为跨上皮阻力(TER)的降低。结论：本研究表明微生物来源的蛋白分解活性具有促进粘膜动态平衡的能力，可能参与炎症性肠病的发病机制。(炎症性肠病2011；17：1189-1200)
Background: Proteolytic degradation of the extracellular matrix, a feature of mucosal homeostasis and tissue renewal, also contributes to the complications of intestinal inflammation. Whether this proteolytic activity is entirely host-derived, or, in part, produced by the gut microbiota, is unknown.Methods: We screened the bacterial colonies for gelatinolytic activity from fecal samples of 20 healthy controls, 23 patients with ulcerative colitis, and 18 with Crohn's disease (CD). In addition, the genes encoding metalloproteases were detected by conventional or real-time polymerase chain reaction (PCR).Results: Gelatinolytic activity was found in approximately one-quarter of samples regardless of the presence of inflammation and without any attempt to enhance the sensitivity of the culture-based screen. This was associated with a diversity of bacteria, particularly in CD, but was predominantly linked with Clostridium perfringens. Culture supernatants from C. perfringens degraded gelatin, azocoll, type I collagen, and basement membrane type IV collagen, but different isolates varied in the degree of proteolytic activity. Results were confirmed by detection of the C. perfringens colA gene (encoding collagenase) in fecal DNA, again regardless of the presence or absence of inflammation. However, the biologic significance and potential implications of microbial-derived proteolytic activity were confirmed by reduced transepithelial resistance (TER) after exposure of rat distal colon to culture supernatants of C. perfringens in Ussing chambers.Conclusions: The study shows that microbial-derived proteolytic activity has the capacity to contribute to mucosal homeostasis and may participate in the pathogenesis of inflammatory bowel disease. (Inflamm Bowel Dis 2011;17:1189-1200)