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Expression of epidermal growth factor, transforming growth factor-α and their receptor in the human oesophagus

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Increasing evidence indicates that epidermal growth factor and transforming growth factor-α are involved in the maintenance of oesophageal mucosal integrity. However, their cellular origin and the exact localization of their receptor in the oesophagus are still unclear. Therefore, we examined the expression of the two growth factors and their shared receptor in the normal human oesophagus at both mRNA and protein level, by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction. In addition to being expressed in the proliferative compartment of the oesophageal epithelium, the receptor was found in a variety of cells, including smooth muscle cells, submucosal gland cells and the epithelium lining their ducts. Immunohistochemically, the pattern of distribution of epidermal growth factor paralleled that of its receptor. In situ hybridization demonstrated epidermal growth factor mRNA expression in the oesophageal epithelium and submucosal glands. Additionally, amplified transcripts of predicted size were detected by reverse transcription-polymerase chain reaction, thus confirming that authentic transcripts of the growth factor exist in the normal human oesophagus. Transforming growth factor-α mRNA and protein expression, while similar to that of epidermal growth factor, predominated in the more differentiated cell layers of the stratified squamous epithelium. These results demonstrate that the normal oesophagus can synthesize both growth factors. Moreover, the peculiar distribution of these peptides and the concomitant expression of their receptor in multiple cell types suggest that the two growth factors may exert diverse physiological functions in the oesophagus and participate in defence and reparative events following mucosal injury.

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References

  • Barnard, J.A., Beauchamp, R.D., Russel, W.E., Dubois, R.N. & Coffey, R.J. (1995) Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology. Gastroenterology108, 564-80.

    Article  PubMed  CAS  Google Scholar 

  • Barrandon, Y. & Green, H. (1987) Cell migration is essential for sustained growth of keratinocyte colonies: the role of transforming growth factor α and epidermal growth factor. Cell50, 1131-7.

    Article  PubMed  CAS  Google Scholar 

  • Bell, G.I., Fong, N.M., Stempien, M.M., Wormsted, M.A., Caput, D.K.L., Urdea, M.S., Rall, L.B. & Sanchez-Pescador, R. (1986) Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization. Nucleic Acids Res.14, 8427-46.

    Article  PubMed  CAS  Google Scholar 

  • Blay, J. & Brown, K.D. (1985) Epidermal growth factor promotes the chemotactic migration of cultured rat intestinal epithelial cells. J. Cell Physiol.124, 107-12.

    Article  PubMed  CAS  Google Scholar 

  • CalabrÒ, A., Orsini, B., Brocchi, A., Falchini, M., Fedi, P. & Surrenti, C. (1990) Gastric juice immunoreactive epidermal growth factor levels in patients with peptic ulcer disease. Am. J. Gastroenterol.85, 404-7.

    PubMed  Google Scholar 

  • CalabrÒ, A., Milani, S., Paladini, I., Orsini, B., Salvadori, G. & Surrenti, C. (1995) Role of epidermal growth factor in peptic ulcer healing. Dig. Dis. Sci.40, 2497-504.

    Article  PubMed  Google Scholar 

  • Carpenter, G. & Cohen, S. (1990) Epidermal growth factor. J. Biol. Chem.265, 7709-12.

    PubMed  CAS  Google Scholar 

  • Carpenter, G. & Wahl, M.L. (1990) The epidermal growth factor family. In Handbook of Experimental Pharmacology. Vol. I. Peptide Growth Factors and their Receptors. (edited by Sporn, M.B. & Roberts, A.B.), pp. 69-171. Berlin: Springer-Verlag.

    Google Scholar 

  • Derynck, R. (1988) Transforming growth factor α. Cell54, 593-5.

    Article  PubMed  CAS  Google Scholar 

  • Dodds, W.J., Hogan, W.J., Hhelm, J.F. & Dent, J. (1981) Pathogenesis of reflux esophagitis. Gastroenterology81, 376-94.

    PubMed  CAS  Google Scholar 

  • Fenoglio-preiser, C.M. (1989) The normal anatomy of the esophagus. In Gastrointestinal Pathology (edited by Fenoglio-preiser, C.M., Lantz, P.E., Listrom, M.B., Davis, M. & Rilke, F.O.), pp. 21-31. New York: Raven Press.

    Google Scholar 

  • Gan, B.S., Hollenberg, M.D., Maccannell, K.L., Lederis, K., Winkler, M.E. & Derynck, R. (1987a) Distinct vascular actions of epidermal growth factor-urogastrone and transforming growth factor α. J. Pharmacol. Exp. Ther.242, 331-7.

    PubMed  CAS  Google Scholar 

  • Gan, B.S., Maccannell, K.L. & Hollenberg, M.D. (1987b) Epidermal growth factor-urogastrone causes vasodilatation in the anesthetized dog. J. Clin. Invest.80, 199-206.

    Article  PubMed  CAS  Google Scholar 

  • Gesualdo, L., Di Paolo, S., CalabrÒ, A., Milani, S., Majorano, E., Ranieri, E., Pannarale, G. & Schena, F.P. (1996) Expression of epidermal growth factor and its receptor in normal and diseased human kidney: an immunohistochemical and in situ hybridization study. Kidney Int.49, 656-65.

    Article  PubMed  CAS  Google Scholar 

  • Hollenberg, M.D. (1994) The acute actions of growth factors in smooth muscle systems. Life Sci.54, 223-35.

    Article  PubMed  CAS  Google Scholar 

  • Hollwarth, M.E., Smith, M., Kvietys, P.R. & Granger, D.N. (1986) Esophageal blood flow in the cat. Gastroenterology90, 622-7.

    PubMed  CAS  Google Scholar 

  • Hradsky, M., Hybasek, I., Cernoch, V. & Juran, J. (1967) Esophageal abnormalities in Sjogren's syndrome. Scand. J. Gastroenterol.2, 200-3.

    Article  PubMed  CAS  Google Scholar 

  • Hui, W.M., Chen, B.W., Chee Kung, A.W., Cho, C.H., Luk, C.T. & Lam, S.K. (1993) Effect of epidermal growth factor on gastric blood flow in rats: possible role in mucosal protection. Gastroenterology104, 1605-10.

    PubMed  CAS  Google Scholar 

  • Jankowski, J., Coghill, G., Tregaskis, B., Hopwood, D. & Wormsley, K.G. (1992a) Epidermal growth factor in the oesophagus. Gut33, 1448-53.

    Article  PubMed  CAS  Google Scholar 

  • Jankowski, J., Murphy, S., Coghill, G., Grant, A., Wormsley, K.G., Sanders, D.S.A., Kerr, M. & Hopwood, D. (1992b) Epidermal growth factor receptor in the oesophagus. Gut33, 439-43.

    Article  PubMed  CAS  Google Scholar 

  • Kajikawa, K., Yasui, W., Sumiyoshi, H., Yoshida, K., Nakayama, H., Ayhan, A., Yokozaki, H., Ito, H. & Tahara, E. (1991) Expression of epidermal growth factor in human tissues. Immunohistochemical and biochemical analysis. Virchows Archiv. A Pathol. Anat.418, 27-32.

    Article  CAS  Google Scholar 

  • Karnes, W.E. Jr. (1994) Epidermal growth factor and transforming growth factor-α. In Gut Peptides: Biochemistry and Physiology. (edited by Walsh J.H. & Dockray, J.), pp. 553-586. New York: Raven Press.

    Google Scholar 

  • Kelly, S.M. & Hunter, J.O. (1990) Epidermal growth factor stimulates synthesis and secretion of mucus glycoproteins in human gastric mucosa. Clin. Sci.79, 425-7.

    PubMed  CAS  Google Scholar 

  • Konturek, S.J. (1988) Role of epidermal growth factor in gastroprotection and ulcer healing. Scand. J. Gastroenterol.23, 129-33.

    Article  PubMed  CAS  Google Scholar 

  • Konturek, S.J., Brzozowski, T., Majka, J., Dembinski, A., Slomiany, A. & Slomiany, B.L. (1992) Transforming growth factor alpha and epidermal growth factor in protection and healing of gastric mucosal injury. Scand. J. Gastroenterol.27, 649-55.

    Article  PubMed  CAS  Google Scholar 

  • Marquardt, H., Hunkapiller, M.W., Hood, L.E. & Todaro, G.J. (1984) Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science223, 1079-82.

    Article  PubMed  CAS  Google Scholar 

  • Meirowitz, R.F., Vengurlekar, S. & Resau, J. (1990) Localisation and characterisation of epidermal growth factor receptors in human epithelium. Gastroenterology98, A38.

    Google Scholar 

  • Merlino, G.T., Xu, Y.H., Ishii, S., Clark, A.J., Semba, K., Toyoshima, K., Yamameto, T. & Pastan, T. (1984) Amplification and enhanced expression of epidermal growth factor receptor gene in A431 human carcinoma cells. Science224, 417-19.

    Article  PubMed  CAS  Google Scholar 

  • Milani, S., Herbst, H., Schuppan, D., Hahn, E.G. & Stein, H. (1989) In situ hybridization for procollagen types I, III, and IV mRNA in normal and fibrotic rat liver: evidence for predominant expression in nonparenchymal liver cells. Hepatology10, 84-92.

    Article  PubMed  CAS  Google Scholar 

  • Milani, S., Herbst, H., Schuppan, D., Stein, H. & Surrenti, C. (1991) Transforming growth factor β1 and β2 are differentially expressed in fibrotic liver disease. Am. J. Pathol.139, 1221-9.

    PubMed  CAS  Google Scholar 

  • Mukaida, H., Yamamoto, Y., Hirai, T.R., Toi, M., Nakamura, T., Yamashita, Y., Kawano, K. & Niimoto, M. (1990) Expression of human epidermal growth factor and its receptor in esophageal cancer. Jpn. J. Surg.20, 275-82.

    Article  PubMed  CAS  Google Scholar 

  • Muramatsu, I., Itoh, H., Lederis, K. & Hollenberg, M.D. (1988) Distinctive actions of epidermal growth factor-urogastrone in isolated smooth muscle preparations from guinea pig stomach: differential inhibition by indomethacin. J. Pharmacol. Exp. Ther.245, 625-31.

    PubMed  CAS  Google Scholar 

  • Namiot, Z., Sarosiek, J., Rourk, R.M., Hetzel, D.P. & Mccallum, R.W. (1994a) Human esophageal secretion: mucosal response to luminal acid and pepsin. Gastroenterology106, 973-81.

    PubMed  CAS  Google Scholar 

  • Namiot, Z., Sarosiek, J., Marcinkiewicz, M., Edmunds, M.C. & Mccallum, R.W. (1994b) Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Dig. Dis. Sci.39, 2523-9.

    Article  PubMed  CAS  Google Scholar 

  • Oates, P.J. (1990) Gastric blood flow and mucosal defence. In Gastric Cytoprotection. (edited by Hollander, D. & Tarnawski, A.S.), pp. 125-65. New York: Plenum Press.

    Google Scholar 

  • Orlando, R.C. (1991) Esophageal epithelial defense against acid injury. J. Clin. Gastroenterol.13(suppl. 2), S1-5.

    PubMed  Google Scholar 

  • Orsini, B., CalabrÓ, A., Milani, S., Grappone, C., Herbst, H. & Surrenti, C. (1993) Localization of epidermal growth factor/transforming growth factor-α receptor in the human gastric mucosa. An immunohistochemical and in situ hybridization study. Virchows Archiv. A Pathol. Anat.423, 57-63.

    Article  CAS  Google Scholar 

  • Poulsen, S.S., Nexo, E., Skov Olsen, P., Hess, J. & Kirkegaard, P. (1986) Immunohistochemical localization of epidermal growth factor in rat and man. Histochemistry85, 389-94.

    Article  PubMed  CAS  Google Scholar 

  • Prigent, S.A. & Lemoine, N.R. (1992) The type 1 (EGFR-related) family of growth factor receptors and their ligands. Prog. Growth Factor Res.4, 1-24.

    Article  PubMed  CAS  Google Scholar 

  • Romano, M., Polk, W.H., Awad, J.A., Arteaga, C.L., Nanney, L.B., Wargovich, M.J., Kraus, E.R., Boland, C.R. & Coffey, R.J. (1992) Transforming growth factor alpha protection against drug-induced injury to the rat gastric mucosa in vivo. J. Clin. Invest.90, 2409-21.

    Article  PubMed  CAS  Google Scholar 

  • Rourk, R.M., Namiot, Z., Edmunds, M.C., Sarosiek, J., Yu, Z. & Mccallum, R.W. (1994) Diminished luminal release of esophageal epidermal growth factor in patients with reflux esophagitis. Am. J. Gastroenterol.89, 1177-94.

    PubMed  CAS  Google Scholar 

  • Sakai, Y., Gray Nelson, K., Snedeker, S., Bossert, N.L., Walker, M.P., Mclaciilan, J. & Diaugustine, R.P. (1994) Expression of epidermal growth factor in suprabasal cells of stratified squamous epithelia: implications for a role in differentiation. Cell. Growth Diff.5, 527-35.

    PubMed  CAS  Google Scholar 

  • Sarosiek, J., Bilski, J., Murty V.L.N., Slomiany, A. & Slomiany, B.L. (1988) Role of salivary epidermal growth factor in the maintenance of physicochemical characteristics of oral and gastric mucosal mucus coat. Biochem. Biophys. Res. Commun.152, 1421-7.

    Article  PubMed  CAS  Google Scholar 

  • Sarosiek, J., Feng, T. & Mccallum, R.W. (1991) The interrelationship between salivary epidermal growth factor and the functional integrity of the esophageal mucosal barrier in the rat. Am. J. Med. Sci.302, 359-63.

    Article  PubMed  CAS  Google Scholar 

  • Sarosiek, J., Hetzel, D.P., Yu, Z., Piascik, R., Li, L., Rourk, R.M. & Mccallum R.W. (1993) Evidence on secretion of epidermal growth factor by the esophageal mucosa in humans. Am. J. Gastroenterol.88, 1081-7.

    PubMed  CAS  Google Scholar 

  • Sorvillo, J.M., Mccormack, E.S., Yanes, L., Valenzuela, D. & Reynolds, F.H.J. (1990) Preparation and characterization of monoclonal antibodies specific for human transforming growth factor-α. Oncogene5, 377-86.

    PubMed  CAS  Google Scholar 

  • Sottili, M., Sternini, C., Brecha, N.C., Lezoche, E. & Walsh, J.H. (1992) Transforming growth factor α receptor binding sites in the canine gastrointestinal tract. Gastroenterology103, 1427-36.

    PubMed  CAS  Google Scholar 

  • Takahashi, M., Ota, S., Ogura, K., Nakamura, T. & Omata, M. (1995) Hepatocyte growth factor stimulates wound repair of the rabbit esophageal epithelial cells in primary culture. Biochem. Biophys. Res. Commun.216, 298-305.

    Article  PubMed  CAS  Google Scholar 

  • Tarnawski, A., Stachura, J., Durbin, T., Sarfeh, I.J. & Gergely, H. (1992) Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats. Gastroenterology102, 695-8.

    PubMed  CAS  Google Scholar 

  • Thomas, D.M., Nasim, M.M., Gullick, W.J. & Alison, M.R. (1992) Immunoreactivity of transforming growth factor alpha in the normal adult gastrointestinal tract. Gut33, 628-31.

    Article  PubMed  CAS  Google Scholar 

  • Tricoli, J.V., Nakai, H., Byers, M.G., Rall, L.B., Bell, G.I. & Shows, T.B. (1986) The gene for human transforming growth factor alpha is on the short arm of chromosome 2. Cytogenet. Cell. Genet.42, 94-8.

    Article  PubMed  CAS  Google Scholar 

  • Ullrich, A., Coussens, L., Hayflik, J.S., Dull, T.J., Gray, A., Tam, A.W., Lee, J., Yarden, Y., Liberman, T.A., Schlessinger, J., Downward, J., Mayes, E.L.V., Whittle, N., Waterfield, M.D. & Seeburg, P.H. (1984) Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature309, 418-25.

    Article  PubMed  CAS  Google Scholar 

  • Valdez J.H. & Fox, P.C. (1991) Interactions of the salivary and gastrointestinal systems. II. Effects of salivary gland dysfunction on the gastrointestinal tract. Dig. Dis. Sci.9, 210-8.

    Article  CAS  Google Scholar 

  • Vinter-jensen, L., Juhl, C.O., Poulsen, S.S., Djur-huus, J.C., Dajani, E.Z. & Nexo, E. (1995) Chronic administration of epidermal growth factor to pigs induces growth, especially of the urinary tract with accumulation of epithelial glycoconjugates. Lab. Invest.73, 788-93.

    PubMed  CAS  Google Scholar 

  • Wright, N.A., Pike, C. & Elia, G. (1990) Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells. Nature343, 82-5.

    Article  PubMed  CAS  Google Scholar 

  • Yang, S.G. & Hollenberg, M.D. (1991) Distinct receptors for epidermal growth factor-urogastrone in cultured gastric smooth muscle cells. Am. J. Physiol.260, G827-34.

    PubMed  CAS  Google Scholar 

  • Yasui, W., Ji, Z., Kuniyasu, H., Ayhan, A., Yokozaki, H., Ito, H. & Tahara, E. (1992) Expression of transforming growth factor alpha in human tissues: immunohistochemical study and Northern blot analysis. Virchows Archiv. A Pathol. Anat.421, 513-19.

    Article  CAS  Google Scholar 

  • Yeh, J., Rein, M. & Nowak, R. (1991) Presence of messenger ribonucleic acid for epidermal growth factor (EGF) and EGF receptor demonstrable in monolayer cell cultures of myometria and leiomyomata. Fertil. Steril.56, 997-1000.

    PubMed  CAS  Google Scholar 

  • Yoshida, S., Kasuga, S., Hirao, Y., Fuwa, T. & Nagakawa, S. (1987) Effect of biosynthetic human epidermal growth factor on the synthesis and secretion of mucin glycoprotein from primary culture of rabbit fundal mucosa cells. In Vitro Cell Dev. Biol.23, 460-4.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Human Genetic Unit and Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, viale Morgagni 85, 50134, Florence, Italy

    A. Calabro

  2. Institute of Pathologic Anatomy, University of Florence Florence, Italy

    B. Orsini, L. Papi, E. Surrenti, S. Milani & C. Surrenti

  3. Institute of Pathology, Eppendorf University Hospital Hamburg, Germany

    D. Renzi, A. Amorosi & H. Herbst

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  1. A. Calabro
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  2. B. Orsini
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  3. D. Renzi
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  4. L. Papi
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  5. E. Surrenti
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  6. A. Amorosi
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  7. H. Herbst
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  8. S. Milani
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  9. C. Surrenti
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Calabro, A., Orsini, B., Renzi, D. et al. Expression of epidermal growth factor, transforming growth factor-α and their receptor in the human oesophagus. J Mol Hist 29, 745–758 (1997). https://doi.org/10.1023/A:1026469219190

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