Skip to main content

Advertisement

SpringerLink
Log in

Protective Factors of the Gastric and Duodenal Mucosa: An Overview

  • Stomach and Duodenum (J Pisegna, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

The structural and functional integrity of the gastric and duodenal mucosa represents equilibrium between aggressive factors and protective mechanisms. Mucus-buffers-phospholipid layer as pre-epithelial barrier, enhanced by prostaglandins and epidermal growth factor, remains a vanguard of mucosal protection. It maintains a neutral pH at the surface epithelial luminal interface, facing luminal pH dropping to 1.0, i.e., hydrogen ion concentration gradient equal 1,000,000. The surface epithelial cells, elaborating mucins, buffers, phospholipids, prostaglandins, trefoil peptides, peptide growth factor and their receptors, heat shock proteins, cathelicidins, and β-defensins form the second line of defense. Endothelium exerts mucosal protection through production of potent vasodilators like nitric oxide and prostacyclins and through release of angiogenic growth factors, securing adequate blood flow and representing the third and an ultimate line of mucosal protection. This microcirculation is instrumental for supply of oxygen, nitric oxide, hydrogen sulfide and removal of ad hoc generated toxic substances as well as for continuous mucosal cell renewal from progenitor cells, secured by growth factors accompanied by survivin preventing early apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Abdel-Salam OM, Czimmer J, Debreceni A, Szolcsanyi J, Mozsik G. Gastric mucosal integrity: gastric mucosal blood flow and microcirculation. An overview. J Physiol Paris. 2001;95(1-6):105–27.

    Article  CAS  PubMed  Google Scholar 

  2. Slomiany BL, Sarosiek J, Slomiany A. Gastric mucus and the mucosal barrier. Dig Dis (Basel, Switz). 1987;5(3):125–45.

    Article  CAS  Google Scholar 

  3. Tulassay Z, Herszenyi L. Gastric mucosal defense and cytoprotection. Best Pract Res Clin Gastroenterol. 2010;24(2):99–108.

    Article  CAS  PubMed  Google Scholar 

  4. Richardson CT. Pathogenetic factors in peptic ulcer disease. Am J Med. 1985;79(2c):1–7.

    Article  CAS  PubMed  Google Scholar 

  5. Chen X, Oshima T, Shan J, Fukui H, Watari J, Miwa H. Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins. Am J Physiol Gastrointest Liver Physiol. 2012;303(2):G199–208.

    Article  CAS  PubMed  Google Scholar 

  6. Jurgens S, Meyer F, Spechler SJ, Souza R. The role of bile acids in the neoplastic progression of Barrett’s esophagus—a short representative overview. Z Gastroenterol. 2012;50(9):1028–34.

    Article  CAS  PubMed  Google Scholar 

  7. Tarnawski AS, Ahluwalia A, Jones MK. The mechanisms of gastric mucosal injury: focus on microvascular endothelium as a key target. Curr Med Chem. 2012;19(1):4–15. This article presents defense mechanisms of gastric mucosa concentrating on the microvascular endothelial barrier. It also demonstrates the generation of prostaglandins, nitric oxide and various other factors that protect from injury and prevent platelet and leukocyte aggregation.

  8. Tarnawski A, Ahluwalia A, Jones MK. Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms of gastroprotective and ulcer healing actions of antacids. Curr Pharm Des. 2013;19(1):126–32. This article highlights acute gastric mucosal injury and the concept of cytoprotection describing the mucosal protective actions of antacids, thereby causing ulcer healing.

    CAS  PubMed  Google Scholar 

  9. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology. 2008;135(1):41–60.

    Article  CAS  PubMed  Google Scholar 

  10. Matteo F, Luca A, Rocchina C, Marco T, Corrado B. Pathophysiology of gastric ulcer development and healing: Molecular mechanisms and novel therapeutic options. In: Chai J Ed. Peptic Ulcer Disease. ISBN 978-953-307-976-9; 2011:113–42.

  11. Konturek SJ. Mechanisms of gastroprotection. Scand J Gastroenterol Suppl. 1990;174:15–28.

    Article  CAS  PubMed  Google Scholar 

  12. Sarosiek J, Peura DA, Guerrant RL, Marshall BJ, Laszewicz W, Gabryelewicz A, et al. Mucolytic effects of Helicobacter pylori. Scand J Gastroenterol Suppl. 1991;187:47–55.

    Article  CAS  PubMed  Google Scholar 

  13. Sarosiek J, Jensen RT, Maton PN, Peura DA, Harlow D, Feng T, et al. Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: its protective potential. Am J Gastroenterol. 2000;95(5):1158–65.

    Article  CAS  PubMed  Google Scholar 

  14. Glass GB, Slomiany BL. Derangements of biosynthesis, production and secretion of mucus in gastrointestinal injury and disease. Adv Exp Med Biol. 1977;89:311–47.

    Article  CAS  PubMed  Google Scholar 

  15. Slomiany BL, Piasek A, Sarosiek J, Slomiany A. The role of surface and intracellular mucus in gastric mucosal protection against hydrogen ion. Compositional differences. Scand J Gastroenterol. 1985;20(10):1191–6.

    Article  CAS  PubMed  Google Scholar 

  16. Kang JM, Kim N, Kim B, Kim JH, Lee BY, Park JH, et al. Gastroprotective action of Cochinchina momordica seed extract is mediated by activation of CGRP and inhibition of cPLA(2)/5-LOX pathway. Dig Dis Sci. 2009;54(12):2549–60.

    Article  PubMed  Google Scholar 

  17. Allen A, Flemstrom G, Garner A, Kivilaakso E. Gastroduodenal mucosal protection. Physiol Rev. 1993;73(4):823–57.

    CAS  PubMed  Google Scholar 

  18. Porchet N, Aubert JP. [MUC genes: mucin or not mucin? That is the question. Med Sci M/S. 2004;20(5):569–74.

    Google Scholar 

  19. Allen A, Flemstrom G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell Physiol. 2005;288(1):C1–19.

    Article  CAS  PubMed  Google Scholar 

  20. Ho SB, Takamura K, Anway R, Shekels LL, Toribara NW, Ota H. The adherent gastric mucous layer is composed of alternating layers of MUC5AC and MUC6 mucin proteins. Dig Dis Sci. 2004;49(10):1598–606.

    Article  CAS  PubMed  Google Scholar 

  21. Lichtenberger LM. Gastroduodenal mucosal defense. Curr Opin Gastroenterol. 1999;15(6):463–72.

    Article  CAS  PubMed  Google Scholar 

  22. Gindzienski A, Zwierz K, Sarosiek J. The role of mucus and its components in protection and repair within the alimentary tract mucosa: polish experience. J Physiol Pharmacol Off J Pol Physiol Soc. 2003;54 Suppl 3:127–44.

    Google Scholar 

  23. Namiot Z, Sarosiek J, Marcinkiewicz M, Edmunds MC, McCallum RW. Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Dig Dis Sci. 1994;39(12):2523–9.

    Article  CAS  PubMed  Google Scholar 

  24. Silva G, Izabel M, Florenco de Sous FC. Gastric ulcer pathology. In: Chai J Ed. Peptic Ulcer Disease. ISBN 978-953-307-976-9; 2011:3–28.

  25. Sarosiek J, Slomiany A, Slomiany BL. Evidence for weakening of gastric mucus integrity by Campylobacter pylori. Scand J Gastroenterol. 1988;23(5):585–90.

    Article  CAS  PubMed  Google Scholar 

  26. Sarosiek J, Marshall BJ, Peura DA, Hoffman S, Feng T, McCallum RW. Gastroduodenal mucus gel thickness in patients with Helicobacter pylori: a method for assessment of biopsy specimens. Am J Gastroenterol. 1991;86(6):729–34.

    CAS  PubMed  Google Scholar 

  27. Palileo C, Kaunitz JD. Gastrointestinal defense mechanisms. Curr Opin Gastroenterol. 2011;27(6):543–8. This article highlights the gastroduodenal mucosal defenses that enhance mucosal healing, focusing on pathophysiological mechanisms. Furthermore, it also describes elements that contribute to the failure of defense systems.

  28. Thim L, Madsen F, Poulsen SS. Effect of trefoil factors on the viscoelastic properties of mucus gels. Eur J Clin Investig. 2002;32(7):519–27.

    Article  CAS  Google Scholar 

  29. Castro-Combs J, Garcia CJ, Majewski M, Wallner G, Sarosiek J. Impaired viscosity of gastric secretion and its mucin content as potential contributing factors to the development of chronic constipation. Dig Dis Sci. 2014;59(11):2730–4.

    Article  CAS  PubMed  Google Scholar 

  30. Nassini R, Andre E, Gazzieri D, De Siena G, Zanasi A, Geppetti P, et al. A bicarbonate-alkaline mineral water protects from ethanol-induced hemorrhagic gastric lesions in mice. Biol Pharm Bull. 2010;33(8):1319–23.

    Article  CAS  PubMed  Google Scholar 

  31. Takeuchi K, Kita K, Hayashi S, Aihara E. Regulatory mechanism of duodenal bicarbonate secretion: roles of endogenous prostaglandins and nitric oxide. Pharmacol Ther. 2011;130(1):59–70.

    Article  CAS  PubMed  Google Scholar 

  32. Ham M, Akiba Y, Takeuchi K, Montrose MH, Kaunitz JD. Gastroduodenal Mucosal Defense. 2012:1169–208. This chapter summarizes the components of various defense mechanisms in detail including the physicial compositions, pH variations and various regulatory mechanisms.

  33. Werther JL. The gastric mucosal barrier. Mt Sinai J Med N Y. 2000;67(1):41–53.

    CAS  Google Scholar 

  34. Kawano S, Tsuji S. Role of mucosal blood flow: a conceptional review in gastric mucosal injury and protection. J Gastroenterol Hepatol. 2000;15(Suppl):D1–6.

    Article  PubMed  Google Scholar 

  35. Tarnawski AS, Chai J, Jones MK. Esophageal and gastrointestinal microcirculation: essential for mucosal protection, a target for injury, and a critical component of injury and ulcer healing. In: Ishii I, Suematsu M, Tanishita K, Suzuki H, editors. Organ microcirculation: a gateway to diagnostic and therapeutic interventions. Tokyo: Springer Publisher; 2005(13): 49–61.

  36. Bonfanti R, Furie BC, Furie B, Wagner DD. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1989;73(5):1109–12.

    CAS  PubMed  Google Scholar 

  37. Wallace JL. Nitric oxide, aspirin-triggered lipoxins and NO-aspirin in gastric protection. Inflamm Allergy Drug Targets. 2006;5(2):133–7.

    Article  CAS  PubMed  Google Scholar 

  38. Fiorucci S, Distrutti E, Cirino G, Wallace JL. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology. 2006;131(1):259–71.

    Article  CAS  PubMed  Google Scholar 

  39. Abdel-Salam OM, Debreceni A, Mozsik G, Szolcsanyi J. Capsaicin-sensitive afferent sensory nerves in modulating gastric mucosal defense against noxious agents. J Physiol Paris. 1999;93(5):443–54.

    Article  CAS  PubMed  Google Scholar 

  40. Bi LC, Kaunitz JD. Gastroduodenal mucosal defense: an integrated protective response. Curr Opin Gastroenterol. 2003;19(6):526–32.

    Article  PubMed  Google Scholar 

  41. Radi ZA. Gastrointestinal Tract. In: Comparative pathophysiology and toxicology of cyclooxygenases. New Jersey: John Wiley & Sons Publishers; ISBN 9780470577547: 2012.

  42. Lacy ER, Ito S. Rapid epithelial restitution of the rat gastric mucosa after ethanol injury. Lab Invest J Tech Methods Pathol. 1984;51(5):573–83.

    CAS  Google Scholar 

  43. Tarnawski A, Stachura J, Durbin T, Sarfeh IJ, Gergely H. Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats. Gastroenterology. 1992;102(2):695–8.

    CAS  PubMed  Google Scholar 

  44. Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS. Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med. 2002;8(3):289–93.

    Article  CAS  PubMed  Google Scholar 

  45. Dias A, Garcia C, Majewski M, Wallner G, McCallum RW, Poplawski C, et al. Gastric juice prostaglandins and peptide growth factors as potential markers of chronic atrophic gastritis, intestinal metaplasia and gastric cancer: their potential clinical implications based on this pilot study. Dig Dis Sci. 2011;56(11):3220–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Chiou SK, Tanigawa T, Akahoshi T, Abdelkarim B, Jones MK, Tarnawski AS. Survivin: a novel target for indomethacin-induced gastric injury. Gastroenterology. 2005;128(1):63–73.

    Article  CAS  PubMed  Google Scholar 

  47. Montrose MH, Akiba Y, Takeuchi K, Kaunitz JD. Gastroduodenal mucosal defense. In: Johnson LR, Barrett KE, Ghishan FK, Merchant JL, Said HM, Wood JD, editors. Physiology of the Gastrointestinal Tract. 4 th Edition. New York: Elsevier Academic Press; 2006 (1): 1259–91.

  48. Kato S, Aihara E, Yoshii K, Takeuchi K. Dual action of prostaglandin E2 on gastric acid secretion through different EP-receptor subtypes in the rat. Am J Physiol Gastrointest Liver Physiol. 2005;289(1):G64–9.

    Article  CAS  PubMed  Google Scholar 

  49. Cryer B. Mucosal defense and repair: role of prostaglandins in the stomach and duodenum. Gastroenterol Clin N Am. 2001;30(4):877–94.

    Article  CAS  Google Scholar 

  50. Atay S, Tarnawski AS, Dubois A. Eicosanoids and the stomach. Prostaglandins Other Lipid Mediat. 2000;61(3-4):105–24.

    Article  CAS  PubMed  Google Scholar 

  51. Takeuchi K, Kato S, Amagase K. Prostaglandin EP receptors involved in modulating gastrointestinal mucosal integrity. J Pharmacol Sci. 2010;114(3):248–61.

    Article  CAS  PubMed  Google Scholar 

  52. Konturek SJ, Konturek PC, Brzozowski T. Prostaglandins and ulcer healing. J Physiol Pharmacol Off J Pol Physiol Soc. 2005;56 Suppl 5:5–31.

    Google Scholar 

  53. Brzozowski T, Konturek PC, Konturek SJ, Brzozowska I, Pawlik T. Role of prostaglandins in gastroprotection and gastric adaptation. J Physiol Pharmacol Off J Pol Physiol Soc. 2005;56 Suppl 5:33–55.

    Google Scholar 

  54. Peskar BM. Neural aspects of prostaglandin involvement in gastric mucosal defense. J Physiol Pharmacol Off J Pol Physiol Soc. 2001;52(4 Pt 1):555–68.

    CAS  Google Scholar 

  55. Araki H, Ukawa H, Sugawa Y, Yagi K, Suzuki K, Takeuchi K. The roles of prostaglandin E receptor subtypes in the cytoprotective action of prostaglandin E2 in rat stomach. Aliment Pharmacol Ther. 2000;14 Suppl 1:116–24.

    Article  CAS  PubMed  Google Scholar 

  56. Konturek PC, Brzozowski T, Pajdo R, Nikiforuk A, Kwiecien S, Harsch I, et al. Ghrelin-a new gastroprotective factor in gastric mucosa. J Physiol Pharmacol Off J Pol Physiol Soc. 2004;55(2):325–36.

    CAS  Google Scholar 

  57. Brzozowski T, Konturek PC, Drozdowicz D, Konturek SJ, Pawlik M, Sliwowski Z, et al. Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence. Inflammopharmacology. 2005;13(1-3):45–62.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Harathi Yandrapu and Jerzy Sarosiek declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors. With regard to the author’s research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Molecular Medicine Research Laboratory, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX, 79905, USA

    Harathi Yandrapu & Jerzy Sarosiek

Authors
  1. Harathi Yandrapu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jerzy Sarosiek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jerzy Sarosiek.

Additional information

This article is part of the Topical Collection on Stomach and Duodenum

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yandrapu, H., Sarosiek, J. Protective Factors of the Gastric and Duodenal Mucosa: An Overview. Curr Gastroenterol Rep 17, 24 (2015). https://doi.org/10.1007/s11894-015-0452-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-015-0452-2

Keywords

Search

Navigation