Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats.
OBJECTIVE
Previous studies have shown that gastric ulceration stimulates epithelial cell proliferation and overexpression of epidermal growth factor (EGF) and EGF receptor (EGF-R) in the mucosa bordering necrosis. The aim of this study was to investigate whether extracellular signal-regulated kinase (ERK) cascade is involved in the healing of experimental gastric ulcers.


METHODS
We studied EGF-R levels, EGF-R phosphorylation levels, and ERK1 and ERK2 activity in normal and ulcerated rat gastric mucosa. We also examined the effect of Tyrphostin A46 (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above parameters.


RESULTS
During the initial stages of healing (3 and 7 days), ulcerated mucosa showed significant increase (vs. controls) in protein tyrosine kinase activity, EGF-R levels (510% and 550%), EGF-R phosphorylation levels, ERK1 activity (430% and 880%), and ERK2 activity (550% and 990%). Tyrphostin A46 treatment significantly inhibited ulcer healing and reduced EGF-R levels, EGF-R phosphorylation, and ERK1 and ERK2 activity.


CONCLUSIONS
These findings indicate that experimental gastric ulcer healing involves activation of EGF-R-ERK signal transduction pathway.
Pai
R
R
Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Ohta
M
M
Itani
R M
RM
Sarfeh
I J
IJ
Tarnawski
A S
AS
D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013276:Stomach Ulcer / Q000201:enzymology*; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins
D001597:Benzylidene Compounds; D009570:Nitriles; D020032:Tyrphostins; C086599:tyrphostin A46; D014443:Tyrosine; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases