Increased expression of transforming growth factor α precursorsin acute experimental colitis in rats

Background and aim—Epidermal growth factor (EGF)and transforming growth factor α (TGF-α), members of the EGF familyof growth factors, protect rat gastric and colonic mucosa againstinjury. Having shown previously that exogenously applied EGF protects rat colonic mucosa against injury, the aim of the present study was toevaluate the endogenously expressed ligand mediating the protectiveeffect of EGF/TGF-α in vivo.
Methods—In an experimental model oftrinitrobenzene sulphonic acid (TNBS)/ ethanol induced colitis in ratsEGF and TGF-α expression was evaluated using a ribonucleaseprotection assay, northern blot analysis, western blot analysis, and immunohistochemistry.
Results—TGF-α mRNA increased 3-4 times at 4-8hours after induction of colitis and returned to control levels within24 hours. TGF-α immunoreactive protein with a molecular size of about28kDa representing TGF-α precursors increased markedly afterinduction of colitis with a peak at 8-12 hours. No fully processed 5.6 kDa TGF-α protein was detected in normal or inflamed colon tissue. Only a weak signal for EGF mRNA expression was detected in the ratcolon and no EGF protein was observed by immunohistochemistry orwestern blot analysis.
Conclusions—TGF-α precursors are the mainligands for the EGF receptor in acute colitis. It is hypothesised thatTGF-α precursors convey the biological activity of endogenous TGF-αpeptides during mucosal defence and repair.