Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa

Citation
U. Schiemann et al., Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa, SC J GASTR, 36(1), 2001, pp. 23-31
Citations number
46
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
ISSN journal
00365521 → ACNP
Volume
36
Issue
1
Year of publication
2001
Pages
23 - 31
Database
ISI
SICI code
0036-5521(200101)36:1<23:DEOEGF>2.0.ZU;2-M
Abstract
Background: Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regula tive role of the four other widely expressed epidermaI growth factor recept or ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in t he gastric mucosa. Methods: Nineteen patients with Helicobacter pylori-posi tive gastritis and 32 healthy controls were investigated. Mucosal mRNA expr ession of EGF receptor ligands was determined by quantitative PCR before an d after H. pylori eradication. PCR products were analyzed by soft laser sca nning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [I-125] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression. Results: Antral and oxyntic biopsies showed strong mRNA express ions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in N. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastriti s was associated with decreased antral EGF receptor binding compared to hea lthy controls, possibly reflecting reduced autoinduction. Immunohistochemic al analyses localized TGF-alpha in the cytoplasma of gastric epithelial cel ls and revealed its increased expression after H. pylori eradication. Concl usions: The data presented suggest that amphiregulin, heparin binding EGF a nd TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. p ylori infection apparently suppresses their mRNA as well as receptor expres sion that is reversed by H. pylori eradication. This deficiency of the gast roprotective EGF system may contribute to the gastric pathogenicity of H. p ylori infection.