Localization of transforming growth factor α and its receptor in gastric mucosal cells. Implications for a regulatory role in acid secretion and mucosal renewal

Abstract

Transforming growth factor α (TGFα) shares with epidermal growth factor (EGF) structural homology (35%), a common cell-surface membrane receptor (TGFα/EGF receptor), and a nearly identical spectrum of biological activity, including inhibition of gastric acid secretion. Herein, we report expression of TGFα mRNA in normal gastric mucosa of the adult guinea pig, rat, and dog. TGFα mRNA was also detected in matched surgically resected gastric mucosa and adjacent gastric carcinoma from 10 patients, and in gastric mucosa adjacent to a benign ulcer from an additional patient. TGFα protein was quantitated by radioimmunoassay and was present in tumor and adjacent mucosa. TGFα/EGF receptor mRNA was also detected in gastric mucosa from all species studied. Localization of TGFα and TGFα/EGF receptor mRNA expression was examined in samples of unfractionated guinea pig gastric mucosa and from chief cell-enriched and parietal cell-enriched fractions. All samples exhibited TGFα and TGFα/EGF receptor expression. The TGFα signal was greatest in the parietal cell fraction (5.8-fold increase), but was also enhanced in the chief cell fraction (1.9-fold increase) relative to the unfractionated gastric mucosa. Like TGFα expression, TGFα/EGF receptor mRNA expression was most intense in the parietal cell-enriched fraction (7.8-fold increase), but was also increased in the chief cell-enriched fraction (2.7-fold increase) relative to the unfractionated guinea pig gastric mucosa. We conclude that TGFα and TGFα/EGF receptor genes are expressed in normal adult mammalian gastric mucosa. These findings, when interpreted in light of described actions of TGFα and EGF, provide evidence that local production of TGFα could play an important role in the regulation of acid secretion and mucosal renewal in the stomach.