Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa.
BACKGROUND
Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regulative role of the four other widely expressed epidermal growth factor receptor ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in the gastric mucosa.


METHODS
Nineteen patients with Helicobacter pylori-positive gastritis and 32 healthy controls were investigated. Mucosal mRNA expression of EGF receptor ligands was determined by quantitative PCR before and after H. pylori eradication. PCR products were analyzed by soft laser scanning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [125I] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression.


RESULTS
Antral and oxyntic biopsies showed strong mRNA expressions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in H. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastritis was associated with decreased antral EGF receptor binding compared to healthy controls, possibly reflecting reduced autoinduction. Immunohistochemical analyses localized TGF-alpha in the cytoplasma of gastric epithelial cells and revealed its increased expression after H. pylori eradication.


CONCLUSIONS
The data presented suggest that amphiregulin, heparin binding EGF and TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. pylori infection apparently suppresses their mRNA as well as receptor expression that is reversed by H. pylori eradication. This deficiency of the gastroprotective EGF system may contribute to the gastric pathogenicity of H. pylori infection.
Schiemann
U
U
Medical Policlinic, University of Munich, Germany. uweschiemann@pk.-i.med.uni.muenchen.de
Konturek
J W
JW
Osterhoff
M
M
Assert
R
R
Rembiasz
K
K
Pfeiffer
D
D
Schatz
H
H
Domschke
W
W
Pfeiffer
A
A
D000328:Adult; D066258:Amphiregulin; D066259:Betacellulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000096:biosynthesis; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D058851:GPI-Linked Proteins; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology; D006023:Glycoproteins / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis
C587848:AREG protein, human; D066258:Amphiregulin; C587851:BTC protein, human; D066259:Betacellulin; D066255:EGF Family of Proteins; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D006133:Growth Substances; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C070636:TDGF1 protein, human; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors