Transforming growth factor-alpha (TGF-alpha) levels in human proximal gastrointestinal epithelium. Effect of mucosal injury and acid inhibition.

TGF-α inhibits gastric acid secretion andmay play an important role in epithelial repair. Wequantitated regional levels of TGF-α in the humanproximal gastrointestinal tract and determined whether they are affected by acid suppression oraspirin-induced injury. Ten healthy volunteers werestudied. After baseline endoscopy with biopsy, fiverandomly received no treatment, aspirin, omeprazole, orcimetidine for one week. Endoscopy was repeated and priorunhealed biopsy sites quantitated. TGF-α levelswere measured by RIA. Five additional subjects thencompleted an extended protocol of three weeks' duration. All subjects were free of H. pylori infection.TGF-α levels in the antrum, 34.76 ± 5.54 pgTGF-α/μg DNA were threefold higher than in thegastric body and duodenum (11.03 ± 2.60 and 10.41± 1.64 respectively, P < 0.01). The number of unhealed sites inthe aspirin group was significantly greater than in thecontrol or acid inhibition groups; however, TGF-αlevels were not different from the surrounding mucosa. TGF-α increased in the controls afterbiopsy; the increase was significant in the body at week2 only. Aspirin significantly increased TGF-αlevels in the gastric body and duodenum after one week. The rise in antral TGF-α appeared delayedand blunted by the aspirin treatment compared tocontrol. There was no relationship between the number ofvisible biopsy sites, degree of aspirin-induced injury, and the TGF-α level. Acid suppression wasassociated with a significant increase in TGF-α inthe gastric body and antrum at one week. Immunochemicalstaining did not demonstrate differences inproliferation in any treatment group compared to controls.TGF-α levels vary by location in the proximalgastrointestinal tract, with significantly greaterlevels in the antrum. After biopsy, TGF-α levelsincrease; short-term aspirin and acid inhibitors modulatethis effect. Aspirin significantly impaired the healingof endoscopic biopsies in the antrum; however, this wasnot associated with changes in TGF-α levels. TGF-α levels did not change in responseto acid secretory state. Further studies of mucosallevels of TGF-α in response to aspirin-inducedinjury in humans appear warranted. [ABSTRACT FROM AUTHOR]