Increased expression of epidermal growth factor-receptor in an experimental model of colitis in rats.
BACKGROUND
Epidermal growth factor and related proteins share some structural homology and bind to one common receptor. We have shown previously that exogenously applied EGF protects colonic mucosa against injury in an experimental model of colitis in rats and that the endogenously expressed ligands for the EGF-receptor are predominantly transforming growth factor alpha precursors. The aim of our present study was to evaluate the EGF-receptor expression in response to mucosal injury in the same model of colitis.


METHODS
The trinitrobenzene sulphonic acid (TNBS)/ethanol-induced model of colitis in rats was used and EGF-receptor expression was evaluated using ribonuclease protection assay and Western blot analysis. The extent of mucosal injury and inflammation was characterized by using a microscopic and macroscopic damage score and by estimation of the myeloperoxidase activity in colonic specimens.


RESULTS
Irritation of the colonic mucosa leads to severe colonic inflammation with tissue oedema, erosions and mucosal ulcers and to a significant increase in myeloperoxidase activity expressed by neutrophil granulocytes and macrophages. A significant increase in EGF-receptor mRNA expression was obtained at 8-24 h followed by an increased expression of the EGF-receptor protein at 1-5 days after the induction of colitis. On Western blot analysis only one immunoreactive band with a molecular weight of approximately 170 kDa was detected.


CONCLUSIONS
Mucosal inflammation leads to a significant increase in the EGF-receptor expression in the early phases of colitis. These findings support our hypothesis that EGF and related proteins and their common receptor play a pivotal role in mucosal defence and repair.
Hoffmann
P
P
Division of Gastroenterology, Harbor UCLA Medical Center, Torrance, California, USA.
Reinshagen
M
M
Zeeh
J M
JM
Lakshmanan
J
J
Wu
V S
VS
Goebell
H
H
Gerken
G
G
Eysselein
V E
VE
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D008297:Male; D023282:Nuclease Protection Assays; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D012333:RNA, Messenger; D009195:Peroxidase; D066246:ErbB Receptors