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
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.