Jeremy, A.H.T.; Aboshkiwa, M.A.; Dixon, M.F.; Robinson, P.A.; Crabtree, J.E.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA34
Academic Journal
Introduction: Chronic H pylori infection in the Mongolian gerbil has been demonstrated to result in gastric cancer. To gain a greater understanding of the mechanisms involved, this study investigated the effects of infection on gastric expression of growth factors. Methods: Male Mongolian gerbils were orally infected three times with H pylori SS1 strain. Infected gerbils (n = 20) and controls (n = 17) were sacrificed at 36 and 62 weeks post-infection (p.i). Gastric mucosa was snap frozen for analysis of growth factor transcripts by RT-PCR. Cross-species PCR and sequencing was used to identify gerbil transcripts for heparin-binding epidermal growth factor (HB-EGF) and transforming growth factor alpha (TGFα). The ratio of growth factors to β-actin was determined by computer image analysis. In addition, HB-EGF Iocalisation was detected by immunohistochemistry. Results: All infected gerbils had chronic gastritis, with more severe pathology and corpus atrophy observed in the 62 week infected animals. Uninfected controls exhibited an age-related increase in transcripts of both HB-EGF (36 week 1.1 ± 0.19 v 62 week 2.1 ± 0.17, p < 0.01) and TGFα (36 week 1.57±0.195 v9 62 week 2.28 ±0.15, p < 0.02). H pylori infection was associated with significantly (p < 0.01) decreased TGFα transcripts at 62 weeks p.i. In infected gerbils HB-EGF also increased with age, but levels were not significantly different to controls. Immunolocalisation showed HB-EGF was present in parietal cells in controls. In contrast, in 62 week H pylori infected gerbils with corpus atrophy HB-EGF was Iocalised in gastric epithelial cells. Conclusions: In the gerbil there are age related increases in gastric growth factor expression. Gastric TGFα but not HB-EGF, was decreased in long term chronic H pylori infection. In H pylori induced corpus atrophy, the presence of HB-EGF in the gastric epithelial cells may play an important role in epithelial...


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