The effects of water extracts of CagA positive or negative Helicobacter pylori on proliferation, apoptosis and connexin formation in acetic acid-induced gastric ulcer of rats.
OBJECTIVE
To investigate the influence of water extracts of CagA-positive or -negative Helicobacter pylori on healing of chronic gastric ulcers and on connexin formation, proliferation and apoptosis, in acetic acid-induced chronic gastric ulcers in rats.


METHODS
Acetic acid was used to induce chronic gastric ulcers in rats, and a water extract of H. pylori was given by mouth every day. Connexin 32 formation was assessed using Western blotting as previously described. The frequencies of proliferating cell nuclear antigen staining and of TdT-mediated dUTP-biotin nick end labelling were examined.


RESULTS
In untreated rats, acetic acid-induced gastric ulcers healed after 14 days and the electrophoretic band corresponding to connexin 32 appeared 4 days after ulcer induction. Treatment with a water extract of H. pylori delayed ulcer healing, with the ulcers remaining unhealed even on the 14th day; healing was delayed more when treatment was with an extract of CagA-positive rather than CagA-negative H. pylori. Connexin 32 appeared earlier when treatment was with a CagA-negative rather than a CagA-positive extract, but in both cases later than in the untreated control group. Proliferating cell nuclear antigen labelling on the fourth day was seen in 14.5% +/- 1.6% of mucosal cells of control group, but in 35.9% +/- 1.4% and 36.5% +/- 1.4% of mucosal cells treated with either VacA(+)CagA(-) and VacA(+)CagA(+) H. pylori extract, respectively. Furthermore, extracts of both H. pylori strains, especially VacA(+)Cag(+) H. pylori promoted apoptosis.


CONCLUSIONS
A water extract of H. pylori increased both proliferation and apoptosis, which are related to exacerbation and healing of ulcer as well as appearance of connexin 32.
Mine
T
T
Department of Internal Medicine, University of Tokyo School of Medicine, Japan. mine-tky@umin.ac.jp
Endo
C
C
Kushima
R
R
Kushima
W
W
Kobayashi
I
I
Muraoka
H
H
Taki
R
R
Fujita
T
T
D019342:Acetic Acid; D000818:Animals; D000942:Antigens, Bacterial; D017209:Apoptosis; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics*; D015153:Blotting, Western; D002455:Cell Division; D017630:Connexins / Q000096:biosynthesis*; D016480:Helicobacter pylori; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology; D000097002:Gap Junction beta-1 Protein
D019342:Acetic Acid; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D017630:Connexins; D000097002:Gap Junction beta-1 Protein; C080866:cagA protein, Helicobacter pylori