Adaptation of the gastric epithelium to injury is maintained in vitro and is associated with increased TGF-alpha expression.
Adaptation is the name given to the progressive decrease in gastric mucosal damage following repeated dosing with damaging agents. This study aimed to determine whether adaptation is an intrinsic property of the gastric epithelium and the role in the development of this process of TGF alpha. Rats were given either one or six daily doses of 10 mg/kg diclofenac or six daily doses of vehicle only (1% methylcellulose). On the 7th day, antral mucosa was taken for organ culture and loaded with [51Cr]. Explants were challenged with ethanol and damage quantified by [51Cr] release. In a separate experiment, rats were dosed as above and the gastric mucosa was extracted and TGF alpha quantified by RIA. The rate of [51Cr] release was significantly lower after ethanol injury in explants from rats previously adapted to diclofenac (9.2 +/- 2.5%) compared with those exposed to a single damaging dose of diclofenac (25.9 +/- 3.5%) or vehicle only (26.4 +/- 3.3%; P < 0.01; ANOVA). The concentration of TGF alpha was significantly higher in the gastric epithelium of rats adapted to diclofenac than other groups (P < 0.05; t-test). Cross adaptation of the gastric mucosa to injury has therefore been demonstrated in antral mucosal explants in organ culture while TGF alpha peptide expression is elevated in the adapted gastric mucosa. These findings suggest that adaptation is an inherent property of the gastric epithelium and it is likely that TGF alpha may play a role in its maintenance.
Doljanin
K
K
University of Melbourne Department of Medicine, Western Hospital, Australia.
Skeljo
M V
MV
Yeomans
N D
ND
Giraud
A S
AS
D000222:Adaptation, Physiological; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D004008:Diclofenac / Q000009:adverse effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000431:Ethanol / Q000009:adverse effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009924:Organ Culture Techniques; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016211:Transforming Growth Factor alpha; D004008:Diclofenac; D000431:Ethanol