Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils.
OBJECTIVE
Human colonization with Helicobacter pylori increases the risk for distal gastric adenocarcinoma, possibly by altering gastric epithelial cell cycle events and/or gastrin secretion. This study aimed to determine whether H. pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma.


METHODS
Mongolian gerbils were challenged with H. pylori wild-type or isogenic cagA(-) and vacA(-) mutants, and apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined by radioimmunoassay.


RESULTS
Gastric epithelial cell turnover was no different after infection with the wild-type, cagA(-), or vacA(-) strains. H. pylori infection significantly increased antral apoptosis 2-4 weeks after challenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation, but then decreased by 40 weeks. Antral proliferation was significantly related to serum gastrin levels, whereas antral apoptosis was inversely related to acute inflammation and lymphoid follicles.


CONCLUSIONS
In H. pylori-infected gerbils, enhanced antral apoptosis is an early and transient cell cycle event. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth in H. pylori-colonized mucosa may be mediated by gastrin-dependent mechanisms.
Peek
R M
RM
Division of Gastroenterology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279, USA. richard.peek@mcmail.vandetbilt.edu
Wirth
H P
HP
Moss
S F
SF
Yang
M
M
Abdalla
A M
AM
Tham
K T
KT
Zhang
T
T
Tang
L H
LH
Modlin
I M
IM
Blaser
M J
MJ
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004847:Epithelial Cells / Q000473:pathology; D005755:Gastrins / Q000378:metabolism*; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D009154:Mutation; D018709:Statistics, Nonparametric; D013270:Stomach / Q000382:microbiology / Q000473:pathology*; D014774:Virulence
D005755:Gastrins