Bebb J R, Letley D P, Thomas R J, Aviles F, Collins H M, Watson S A, Hand N M, Zaitoun A, Atherton J C
Division of Gastroenterology and Institute of Infections, Immunity, and Inflammation, University Hospital, Nottingham, UK.
Gut. 2003 Oct;52(10):1408-13. doi: 10.1136/gut.52.10.1408.
Matrix metalloproteinase-7 (MMP-7) is important in normal and pathological remodelling of epithelial-matrix interactions, and is upregulated in gastric cancer. Helicobacter pylori infection is the first stage in gastric carcinogenesis, and therefore our aim was to determine if H pylori upregulated gastric MMP-7 expression and if this was affected by strain virulence.
We took gastric biopsy specimens at endoscopy from H pylori infected (n = 17) and uninfected (n = 18) patients and assessed MMP-7 expression by ELISA, real time polymerase chain reaction (PCR), and immunohistochemistry (concentrating on epithelial cells in the proliferative zone). We PCR typed H pylori for cagE and vacA. We performed H pylori/cell line coculture studies with wild-type pathogenic and non-pathogenic H pylori strains and with CagE(-) and VacA(-) isogenic mutants.
Gastric biopsy specimens from H pylori+ patients expressed higher levels of MMP-7 at the protein and mRNA levels in the antrum and corpus (for example, by ELISA: H pylori+ 0.182 OD units vH pylori- 0.059; p = 0.009 antrum). Epithelial cells from H pylori+ patients stained more intensely for MMP-7 than those from uninfected patients, including in the proliferative zone containing pluripotent cells (p<0.03 antrum, p<0.04 body). Upregulation of MMP-7 in epithelial cells was confirmed at the protein and mRNA levels by H pylori/cell line coculture. These experiments also showed that MMP-7 upregulation was dependent on an intact H pyloricag pathogenicity island but not on the vacuolating cytotoxin.
We speculate that increased expression of MMP-7 in H pylori gastritis may contribute to gastric carcinogenesis.
基质金属蛋白酶-7（MMP-7）在正常及病理状态下上皮-基质相互作用的重塑过程中发挥重要作用，且在胃癌中表达上调。幽门螺杆菌感染是胃癌发生的起始阶段，因此我们旨在确定幽门螺杆菌是否上调胃MMP-7的表达，以及这是否受菌株毒力的影响。
在内镜检查时，我们从幽门螺杆菌感染患者（n = 17）和未感染患者（n = 18）获取胃活检标本，通过酶联免疫吸附测定（ELISA）、实时聚合酶链反应（PCR）及免疫组织化学（聚焦于增殖区的上皮细胞）评估MMP-7的表达。我们对幽门螺杆菌进行cagE和vacA的PCR分型。我们用野生型致病性和非致病性幽门螺杆菌菌株以及CagE(-)和VacA(-)同基因突变体进行幽门螺杆菌/细胞系共培养研究。
幽门螺杆菌阳性患者的胃活检标本在胃窦和胃体的蛋白质及mRNA水平上表达更高水平的MMP-7（例如，通过ELISA：幽门螺杆菌阳性0.182光密度单位对幽门螺杆菌阴性0.059；胃窦p = 0.009）。幽门螺杆菌阳性患者的上皮细胞MMP-7染色比未感染患者的上皮细胞更强烈，包括在含有多能细胞的增殖区（胃窦p<0.03，胃体p<0.04）。通过幽门螺杆菌/细胞系共培养在蛋白质和mRNA水平上证实了上皮细胞中MMP-7的上调。这些实验还表明MMP-7的上调依赖于完整的幽门螺杆菌cag致病岛，而不依赖于空泡毒素。
我们推测幽门螺杆菌胃炎中MMP-7表达增加可能有助于胃癌的发生。
