Adaptation of the gastric epithelium to injury is maintained in vitro and is associated with increased TGF-α 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 TGFα. 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 TGFα 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 TGFα 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 TGFα 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 TGFα may play a role in its maintenance.