Increased expression of transforming growth factor alpha precursors in acute experimental colitis in rats.
OBJECTIVE
Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha), members of the EGF family of growth factors, protect rat gastric and colonic mucosa against injury. Having shown previously that exogenously applied EGF protects rat colonic mucosa against injury, the aim of the present study was to evaluate the endogenously expressed ligand mediating the protective effect of EGF/TGF-alpha in vivo.


METHODS
In an experimental model of trinitrobenzene sulphonic acid (TNBS)/ethanol induced colitis in rats EGF and TGF-alpha expression was evaluated using a ribonuclease protection assay, northern blot analysis, western blot analysis, and immunohistochemistry.


RESULTS
TGF-alpha mRNA increased 3-4 times at 4-8 hours after induction of colitis and returned to control levels within 24 hours. TGF-alpha immunoreactive protein with a molecular size of about 28 kDa representing TGF-alpha precursors increased markedly after induction of colitis with a peak at 8-12 hours. No fully processed 5.6 kDa TGF-alpha protein was detected in normal or inflamed colon tissue. Only a weak signal for EGF mRNA expression was detected in the rat colon and no EGF protein was observed by immunohistochemistry or western blot analysis.


CONCLUSIONS
TGF-alpha precursors are the main ligands for the EGF receptor in acute colitis. It is hypothesised that TGF-alpha precursors convey the biological activity of endogenous TGF-alpha peptides during mucosal defence and repair.
Hoffmann
P
P
Division of Gastroenterology, Harbor UCLA Medical Center, Torrance 90509, USA.
Zeeh
J M
JM
Lakshmanan
J
J
Wu
V S
VS
Procaccino
F
F
Reinshagen
M
M
McRoberts
J A
JA
Eysselein
V E
VE
D000208:Acute Disease; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D017931:DNA Primers; D011498:Protein Precursors; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D000431:Ethanol; D004815:Epidermal Growth Factor; D014302:Trinitrobenzenesulfonic Acid