Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

The role of mucin in GERD and its complications

Nature Reviews Gastroenterology & Hepatology volume 9, pages 55–59 (2012)Cite this article

Subjects

Abstract

Acid, pepsin and other noxious material reach the esophageal mucosa and interact with the luminal aspect of the squamous epithelium. The first protective barrier to these potentially injurious substances is the mucus buffer layer that covers the mucosa. In healthy people, the esophagus has a protective surface adherent mucus gel barrier. Levels of mucin glycoprotein are considerably increased in response to acid and pepsin. A wide spectrum of mucin genes are expressed in normal esophageal mucosa, squamous cell carcinoma of the esophagus, Barrett epithelium and esophageal adenocarcinoma. The mucins MUC5AC and MUC6 are expressed to a similar degree in Barrett metaplasia and gastric mucosa, as is MUC2 in Barrett intestinal metaplasia and small bowel mucosa. Increased expression of MUC1 is associated with progression from dysplasia to adenocarcinoma of the esophagus. Thus, mucins have an important role in the defense of esophageal mucosa against the acid, pepsin and bile that are present in the refluxate. Changes in the expression of mucins occur in patients with GERD, and might lead to the development of new drugs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The structure of two mucins.

Similar content being viewed by others

References

  1. Marcinkiewicz, M., Namiot, Z., Edmunds, M. C., McCallum, R. W. & Sarosiek, J. Detrimental impact of acid and pepsin on the rate of luminal release of transforming growth factor alpha. Its potential pathogenetic role in the development of reflux esophagitis. J. Clin. Gastroenterol. 23, 261–268 (1996).

    Article  CAS  Google Scholar 

  2. Sarosiek, J. & McCallum, R. W. What is the secretory potential of submucosal mucous glands within the human gullet in health and disease? Digestion 56 (Suppl. 1), 15–23 (1995).

    Article  CAS  Google Scholar 

  3. Namiot, Z. et al. Modulatory effect of esophageal intraluminal mechanical and chemical stressors on salivary prostaglandin E2 in humans. Am. J. Med. Sci. 313, 90–98 (1997).

    CAS  PubMed  Google Scholar 

  4. Marcinkiewicz, M. et al. Monophasic luminal release of prostaglandin E2 in patients with reflux esophagitis under the impact of acid and acid/pepsin solutions. Its potential pathogenetic significance. J. Clin. Gastroenterol. 21, 268–274 (1995).

    Article  CAS  Google Scholar 

  5. Sarosiek, J. & McCallum, R. W. Do salivary organic components play a protective role in health and disease of the esophageal mucosa? Digestion 56 (Suppl. 1), 32–37 (1995).

    Article  CAS  Google Scholar 

  6. Sarosiek, J. & McCallum, R. W. What role do salivary inorganic components play in health and disease of the esophageal mucosa? Digestion 56 (Suppl. 1), 24–31 (1995).

    Article  CAS  Google Scholar 

  7. Abdulnour-Nakhoul, S. et al. The effect of tegaserod on esophageal submucosal glands bicarbonate and mucin secretion. Dig. Dis. Sci. 53, 2366–2372 (2008).

    Article  CAS  Google Scholar 

  8. Majewski, M. & McCallum, R. W. Results of small intestinal bacterial overgrowth testing in irritable bowel syndrome patients: clinical profiles and effects of antibiotic trial. Adv. Med. Sci. 52, 139–142 (2007).

    CAS  PubMed  Google Scholar 

  9. Sarosiek, J. & McCallum, R. W. Mechanisms of oesophageal mucosal defence. Baillieres Best Pract. Res. Clin. Gastroenterol. 14, 701–717 (2000).

    Article  CAS  Google Scholar 

  10. Dent, J., El-Serag, H. B., Wallander, M. A. & Johansson, S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 54, 710–717 (2005).

    Article  CAS  Google Scholar 

  11. Locke, G. R. 3rd, Talley, N. J., Fett, S. L., Zinsmeister, A. R. & Melton, L. J. 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 112, 1448–1456 (1997).

    Article  Google Scholar 

  12. Sandler, R. S. et al. The burden of selected digestive diseases in the United States. Gastroenterology 122, 1500–1511 (2002).

    Article  Google Scholar 

  13. Namiot, Z., Sarosiek, J., Marcinkiewicz, M., Edmunds, M. C. & McCallum, R. W. Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Dig. Dis. Sci. 39, 2523–2529 (1994).

    Article  CAS  Google Scholar 

  14. Sarosiek, I. et al. Significant increase of esophageal mucin secretion in patients with reflux esophagitis after healing with rabeprazole: its esophagoprotective potential. Dig. Dis. Sci. 54, 2137–2142 (2009).

    Article  CAS  Google Scholar 

  15. Namiot, Z., Sarosiek, J., Rourk, R. M., Hetzel, D. P. & McCallum, R. W. Human esophageal secretion: mucosal response to luminal acid and pepsin. Gastroenterology 106, 973–981 (1994).

    Article  CAS  Google Scholar 

  16. Tanaka, S., Guth, P. H. & Kaunitz, J. D. In vivo microscopic study of oesophagel mucus gel thickness and blood flow during luminal acid challenge in rats. Gastroenterology 110, A274 (1996).

    Google Scholar 

  17. Dixon, J. et al. Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett's esophagus. Am. J. Gastroenterol. 96, 2575–2583 (2001).

    Article  CAS  Google Scholar 

  18. Sonnenberg, A. et al. Salivary secretion in reflux esophagitis. Gastroenterology 83, 889–895 (1982).

    CAS  PubMed  Google Scholar 

  19. Sarosiek, J. et al. The effect of esophageal mechanical and chemical stimuli on salivary mucin secretion in healthy individuals. Am. J. Med. Sci. 308, 23–31 (1994).

    Article  CAS  Google Scholar 

  20. Kinoshita, M., Kume, E., Igarashi, S., Saito, N. & Narita, H. Role of salivary mucin in the protection of rat esophageal mucosa from acid and pepsin-induced injury. Am. J. Physiol. 277, G796–G800 (1999).

    CAS  PubMed  Google Scholar 

  21. Rayment, S. A., Liu, B., Offner, G. D., Oppenheim, F. G. & Troxler, R. F. Salivary mucin: a factor in the lower prevalence of gastroesophageal reflux disease in African-Americans? Am. J. Gastroenterol. 95, 3064–3070 (2000).

    Article  CAS  Google Scholar 

  22. Sarosiek, J., Scheurich, C. J., Marcinkiewicz, M. & McCallum, R. W. Enhancement of salivary esophagoprotection: rationale for a physiological approach to gastroesophageal reflux disease. Gastroenterology 110, 675–681 (1996).

    Article  CAS  Google Scholar 

  23. van Roon, A. H. et al. Impact of gastro-esophageal reflux on mucin mRNA expression in the esophageal mucosa. J. Gastrointest. Surg. 12, 1331–1340 (2008).

    Article  Google Scholar 

  24. Endo, T. et al. Expression of sulfated carbohydrate chain and core peptides of mucin detected by monoclonal antibodies in Barrett's esophagus and esophageal adenocarcinoma. J. Gastroenterol. 33, 811–815 (1998).

    Article  CAS  Google Scholar 

  25. Jauregui, H. O., Davessar, K., Hale, J. H., Kessimian, N. & Cenoz, C. Mucin histochemistry of intestinal metaplasia in Barrett's esophagus. Mod. Pathol. 1, 188–192 (1988).

    CAS  PubMed  Google Scholar 

  26. Guillem, P. et al. Mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus. Int. J. Cancer 88, 856–861 (2000).

    Article  CAS  Google Scholar 

  27. Warson, C. et al. Barrett's esophagus is characterized by expression of gastric-type mucins (MUC5AC, MUC6) and TFF peptides (TFF1 and TFF2), but the risk of carcinoma development may be indicated by the intestinal-type mucin, MUC2. Hum. Pathol. 33, 660–668 (2002).

    Article  CAS  Google Scholar 

  28. Yamamoto, S. et al. Immunohistochemical mucin expression of short-segment Barrett's esophagus. Tokai J. Exp. Clin. Med. 28, 57–63 (2003).

    PubMed  Google Scholar 

  29. Yamamoto, S. et al. Mucin expression and proliferating cell index of esophageal Barrett's adenocarcinoma. Int. J. Mol. Med. 16, 375–380 (2005).

    CAS  PubMed  Google Scholar 

  30. Liu, G. S. et al. Distinction between short-segment Barrett's esophageal and cardiac intestinal metaplasia. World J. Gastroenterol. 11, 6360–6365 (2005).

    Article  Google Scholar 

  31. Glickman, J. N., Shahsafaei, A. & Odze, R. D. Mucin core peptide expression can help differentiate Barrett's esophagus from intestinal metaplasia of the stomach. Am. J. Surg. Pathol. 27, 1357–1365 (2003).

    Article  Google Scholar 

  32. Amano, Y. et al. Prevalence of and risk factors for Barrett's esophagus with intestinal predominant mucin phenotype. Scand. J. Gastroenterol. 41, 873–879 (2006).

    Article  Google Scholar 

  33. Glickman, J. N. et al. Mucin core polypeptide expression in the progression of neoplasia in Barrett's esophagus. Hum. Pathol. 37, 1304–1315 (2006).

    Article  CAS  Google Scholar 

  34. Burjonrappa, S. C. et al. Mucin expression profile in Barrett's, dysplasia, adenocarcinoma sequence in the esophagus. Indian J. Cancer 44, 1–5 (2007).

    Article  CAS  Google Scholar 

  35. Lopes, C. V., Pereira-Lima, J. & Hartmann, A. Expression of mucin-2 and correlation with PAS-alcian blue stain in Barrett's esophagus. Hepatogastroenterology 53, 511–515 (2006).

    CAS  PubMed  Google Scholar 

  36. Song, S. et al. Induction of MUC5AC mucin by conjugated bile acids in the esophagus involves the phosphatidylinositol 3-kinase/protein kinase C/activator protein-1 pathway. Cancer 117, 2386–2397 (2011).

    Article  CAS  Google Scholar 

  37. Brown, I. S., Whiteman, D. C. & Lauwers, G. Y. Foveolar type dysplasia in Barrett esophagus. Mod. Pathol. 23, 834–843 (2010).

    Article  CAS  Google Scholar 

  38. Haggitt, R. C., Reid, B. J., Rabinovitch, P. S. & Rubin, C. E. Barrett's esophagus. Correlation between mucin histochemistry, flow cytometry, and histologic diagnosis for predicting increased cancer risk. Am. J. Pathol. 131, 53–61 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Chen, Y. Y. et al. Significance of acid-mucin-positive nongoblet columnar cells in the distal esophagus and gastroesophageal junction. Hum. Pathol. 30, 1488–1495 (1999).

    Article  CAS  Google Scholar 

  40. Sirigu, F., Capeccioni, S. & Dessi, A. Mucin histochemistry in Barrett's esophagus. Riv. Eur. Sci. Med. Farmacol. 12, 229–232 (1990).

    CAS  PubMed  Google Scholar 

  41. Bogomoletz, W. V. et al. Mucin histochemistry of heterotopic gastric mucosa of the upper esophagus in adults: possible pathogenic implications. Hum. Pathol. 19, 1301–1306 (1988).

    Article  CAS  Google Scholar 

  42. Shet, T., Desai, S., Prabhu, S. & Amarapurkar, D. Mucin histochemistry of esophagus in health and malignancy. Indian J. Gastroenterol. 16, 140–141 (1997).

    CAS  PubMed  Google Scholar 

  43. Hsu, C. Y., Yang, C. F., Lai, C. R. & Chiang, H. Squamous cell carcinoma of esophagus with diffuse mucin-secreting component: a clinicopathologic study. Zhonghua Yi Xue Za Zhi (Taipei) 59, 275–282 (1997).

    CAS  Google Scholar 

  44. Fegelman, E. et al. Squamous cell carcinoma of the esophagus with mucin-secreting component. Mucoepidermoid carcinoma. J. Thorac. Cardiovasc. Surg. 107, 62–67 (1994).

    CAS  PubMed  Google Scholar 

  45. Chong, F. K., Graham, J. H. & Madoff, I. M. Mucin-producing carcinoid (“composite tumor”) of upper third of esophagus: a variant of carcinoid tumor. Cancer 44, 1853–1859 (1979).

    Article  CAS  Google Scholar 

  46. Kushima, R. et al. Pyloric gland adenoma arising in Barrett's esophagus with mucin immunohistochemical and molecular cytogenetic evaluation. Virchows Arch. 446, 537–541 (2005).

    Article  CAS  Google Scholar 

  47. Samuels, T. L. et al. Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux. Ann. Otol. Rhinol. Laryngol. 117, 688–695 (2008).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, 39 Jabotinski Street, Petach Tikva, 49100, Israel

    Yaron Niv

  2. Division of Gastroenterology, Southern Arizona VA Health Care System, 3601 South Sixth Avenue, Tucson, 85723-0001, AZ, USA

    Ronnie Fass

Authors
  1. Yaron Niv
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronnie Fass
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed equally to all aspects of this article.

Corresponding author

Correspondence to Yaron Niv.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niv, Y., Fass, R. The role of mucin in GERD and its complications. Nat Rev Gastroenterol Hepatol 9, 55–59 (2012). https://doi.org/10.1038/nrgastro.2011.211

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2011.211

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing