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

• Published in: The Journal of clinical investigation Vol. 84; no. 3; pp. 1017 - 1023
• Main Authors: BEAUCHAMP, R. D, BARNARD, J. A, MCCUTCHEN, C. M, CHERNER, J. A, COFFEY, R. J. JR
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.09.1989
• Subjects: Adult; Aged; Aged, 80 and over; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Blotting, Northern; Carcinoma - analysis; Carcinoma - secretion; DNA Probes; Dogs; Fundamental and applied biological sciences. Psychology; Gastric Acid - secretion; Gastric Mucosa - metabolism; Gastric Mucosa - physiology; Guinea Pigs; Humans; Middle Aged; mucosa; Protein hormones. Growth factors. Cytokines; Proteins; Rats; Receptor, Epidermal Growth Factor - isolation & purification; Receptor, Epidermal Growth Factor - physiology; RNA, Messenger - isolation & purification; stomach; Stomach Neoplasms - analysis; Stomach Neoplasms - secretion; Transforming Growth Factors - isolation & purification; Transforming Growth Factors - metabolism; Transforming Growth Factors - physiology; Molecular hybridization; Transforming growth factor; Mucosa; Northern blotting; Vertebrata; Gastric wall; Epidermal growth factor; Mammalia; Messenger RNA; Polypeptide; Radioimmunoassay; Localization; Growth factor; Biological receptor
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci114223

Transforming growth factor alpha (TGF alpha) shares with epidermal growth factor (EGF) structural homology (35%), a common cell-surface membrane receptor (TGF alpha/EGF receptor), and a nearly identical spectrum of biological activity, including inhibition of gastric acid secretion. Herein, we report expression of TGF alpha mRNA in normal gastric mucosa of the adult guinea pig, rat, and dog. TGF alpha 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. TGF alpha protein was quantitated by radioimmunoassay and was present in tumor and adjacent mucosa. TGF alpha/EGF receptor mRNA was also detected in gastric mucosa from all species studied. Localization of TGF alpha and TGF alpha/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 TGF alpha and TGF alpha/EGF receptor expression. The TGF alpha 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 TGF alpha expression, TGF alpha/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 TGF alpha and TGF alpha/EGF receptor genes are expressed in normal adult mammalian gastric mucosa. These findings, when interpreted in light of described actions of TGF alpha and EGF, provide evidence that local production of TGF alpha could play an important role in the regulation of acid secretion and mucosal renewal in the stomach.