Matrix metalloproteinase-7 and premalignant host responses in Helicobacter pylori-infected mice.
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.
Ogden
Seth R
SR
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2279, USA.
Noto
Jennifer M
JM
Allen
Shannon S
SS
Patel
Dilan A
DA
Romero-Gallo
Judith
J
Washington
M Kay
MK
Fingleton
Barbara
B
Israel
Dawn A
DA
Lewis
Nuruddeen D
ND
Wilson
Keith T
KT
Chaturvedi
Rupesh
R
Zhao
Zhiguo
Z
Shyr
Yu
Y
Peek
Richard M
RM
D000230:Adenocarcinoma / Q000201:enzymology / Q000382:microbiology; D000818:Animals; D005753:Gastric Mucosa / Q000201:enzymology / Q000382:microbiology; D005756:Gastritis / Q000201:enzymology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000201:enzymology*; D016480:Helicobacter pylori; D007150:Immunohistochemistry; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000201:enzymology* / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000382:microbiology
D020783:Matrix Metalloproteinase 7