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Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa

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Abstract

Trefoil factor 2 (TFF2) is mucin associated peptide that has a mucosal barrier function in addition to participating in repair and healing. We examined the localization of TFF2 and gastric mucins in gastric mucous cells, the surface mucous gel layer (SMGL) adherent to normal gastric mucosa, and in the mucoid cap covering gastric erosions. Carnoy’s solution, or formalin/picric acid-fixed paraffin embedded materials from resected stomachs and formalin-fixed paraffin embedded gastric biopsy materials were used. Sections were immunostained for the TFF2 and histochemically stained for gastric mucins. In addition, thick sectioned gastric mucosa fixed in Carnoy’s solution were stained with FITC-labeled GSA-II lectin specific for gland mucous cell mucin and examined for three-dimensional images of the SMGL using a confocal laser scanning microscope. The TFF2 and gland mucous cell mucin were found intermixed together in the gastric gland mucous cells, in the SMGL in laminated layers, and in the mucoid cap. A laminated arrangement of continuous sheets of gland mucous cell mucin in the SMGL was demonstrated in the three-dimensional images. Co-localization of the TFF2 with gland mucous cell mucin suggests a physical interaction between the TFF2 and gland mucous cell mucin. The TFF2 trapped in the adherent mucins may be responsible for mucosal defense, healing, and repair.

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References

  • Allen A, Hutton DA, Leonard AJ, Pearson JP, Sellers LA (1986) The role of mucus in the protection of the gastroduodenal mucosa. Scand J Gastroenterol Suppl 125:71–78

    PubMed  CAS  Google Scholar 

  • Allen A, Flemstrom G, Garner A, Kivilaakso E (1993) Gastroduodenal mucosal protection. Physiol Rev 73:823–857

    PubMed  CAS  Google Scholar 

  • Arai K, Ota H, Hidaka E, Hayama M, Sano K, Sugiyama A, Akamatsu T, Katsuyama T (2004) Histochemical, ultrastructural, and three-dimensional observation of smooth muscle cells in human gastric mucosa. Histochem Cell Biol 121:229–237

    Article  PubMed  CAS  Google Scholar 

  • Babyatsky MW, deBeaumont M, Thim L, Podolsky DK (1996) Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats. Gastroenterology 110:489–497

    Article  PubMed  CAS  Google Scholar 

  • Dignass A, Lynch-Devaney K, Kindon H, Thim L, Podolsky DK (1994) Trefoil peptides promote epithelial migration through a transforming growth factor beta-independent pathway. J Clin Invest 94:376–383

    Article  PubMed  CAS  Google Scholar 

  • Hanby AM, Poulsom R, Singh S, Elia G, Jeffery RE, Wright NA (1993) Spasmolytic polypeptide is a major antral peptide: distribution of the trefoil peptides human spasmolytic polypeptide and pS2 in the stomach. Gastroenterology 105:1110–1116

    PubMed  CAS  Google Scholar 

  • Ho SB, Roberton AM, Shekels LL, Lyftogt CT, Niehans GA, Toribara NW (1995) Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression. Gastroenterology 109:735–747

    Article  PubMed  CAS  Google Scholar 

  • Ho SB, Takamura K, Anway R, Shekels LL, Toribara NW, Ota H (2004) The adherent gastric mucous layer is composed of alternating layers of MUC5AC and MUC6 mucin proteins. Dig Dis Sci 49:1598–1606

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann W (2004) Trefoil factor family (TFF) peptides: regulators of mucosal regeneration and repair, and more. Peptides 25:727–730

    Article  PubMed  CAS  Google Scholar 

  • Ishihara K, Kurihara M, Goso Y, Ota H, Katsuyama T, Hotta K (1996a) Establishment of monoclonal antibodies against carbohydrate moiety of gastric mucins distributed in the different sites and layers of rat gastric mucosa. Glycoconj J 13:857–864

    Article  CAS  Google Scholar 

  • Ishihara K, Kurihara M, Goso Y, Urata T, Ota H, Katsuyama T, Hotta K (1996b). Peripheral alpha-linked N-acetylglucosamine on the carbohydrate moiety of mucin derived from mammalian gastric gland mucous cells: epitope recognized by a newly characterized monoclonal antibody. Biochem J 318(Pt 2):409–416

    Google Scholar 

  • Jeffrey GP, Oates PS, Wang TC, Babyatsky MW, Brand SJ (1994) Spasmolytic polypeptide: a trefoil peptide secreted by rat gastric mucous cells. Gastroenterology 106:336–345

    PubMed  CAS  Google Scholar 

  • Jorgensen KH, Thim L, Jacobsen HE (1982) Pancreatic spasmolytic polypeptide (PSP): I. Preparation and initial chemical characterization of a new polypeptide from porcine pancreas. Regul Pept 3:207–219

    Article  PubMed  CAS  Google Scholar 

  • Komuro Y, Ishihara K, Ishii K, Ota H, Katsuyama T, Saigenji K, Hotta K (1992) A separating method for quantifying mucus glycoprotein localized in the different layer of rat gastric mucosa. Gastroenterol Jpn 27:466–472

    PubMed  CAS  Google Scholar 

  • Konturek PC, Brzozowski T, Konturek SJ, Elia G, Wright N, Sliwowski Z, Thim L, Hahn EG (1997) Role of spasmolytic polypeptide in healing of stress-induced gastric lesions in rats. Regul Pept 68: 71–79

    Article  PubMed  CAS  Google Scholar 

  • Kouznetsova I, Peitz U, Vieth M, Meyer F, Vestergaard EM, Malfertheiner P, Roessner A, Lippert H, Hoffmann W (2004) A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa. Cell Tissue Res 316:155–165

    Article  Google Scholar 

  • Longman RJ, Douthwaite J, Sylvester PA, Poulsom R, Corfield AP, Thomas MG, Wright NA (2000) Coordinated localization of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa. Gut 47:792–800

    Article  PubMed  CAS  Google Scholar 

  • McKenzie C, Thim L, Parsons ME (2000) Topical and intravenous administration of trefoil factors protect the gastric mucosa from ethanol-induced injury in the rat. Aliment Pharmacol Ther 14:1033–1040

    Article  PubMed  CAS  Google Scholar 

  • Newton JL, Allen A, Westley BR, May FE (2000) The human trefoil peptide, TFF1, is present in different molecular forms that are intimately associated with mucus in normal stomach. Gut 46:312–320

    Article  PubMed  CAS  Google Scholar 

  • Ota H, Katsuyama T (1992) Alternating laminated array of two types of mucin in the human gastric surface mucous layer. Histochem J 24:86–92

    Article  PubMed  CAS  Google Scholar 

  • Ota H, Katsuyama T, Ishii K, Nakayama J, Shiozawa T, Tsukahara Y (1991) A dual staining method for identifying mucins of different gastric epithelial mucous cells. Histochem J 23:22–28

    Article  PubMed  CAS  Google Scholar 

  • Playford RJ, Marchbank T, Chinery R, Evison R, Pignatelli M, Boulton RA, Thim L, Hanby AM (1995) Human spasmolytic polypeptide is a cytoprotective agent that stimulates cell migration. Gastroenterology 108:108–116

    Article  PubMed  CAS  Google Scholar 

  • Podolsky DK, Lynch-Devaney K, Stow JL, Oates P, Murgue B, DeBeaumont M, Sands BE, Mahida YR (1993) Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion. J Biol Chem 268:6694–6702

    PubMed  CAS  Google Scholar 

  • Ruchaud-Sparagano MH, Westley BR, May FE (2004) The trefoil protein TFF1 is bound to MUC5AC in human gastric mucosa. Cell Mol Life Sci 61:1946–1954

    Article  PubMed  CAS  Google Scholar 

  • Sands BE, Podolsky DK (1996) The trefoil peptide family. Annu Rev Physiol 58:253–273

    Article  PubMed  CAS  Google Scholar 

  • Thim L (1997) Trefoil peptides: from structure to function. Cell Mol Life Sci 53:888–903

    Article  PubMed  CAS  Google Scholar 

  • Thim L, Madsen F, Poulsen SS (2002) Effect of trefoil factors on the viscoelastic properties of mucus gels. Eur J Clin Invest 32:519–527

    Article  PubMed  CAS  Google Scholar 

  • Tomasetto C, Rio MC, Gautier C, Wolf C, Hareuveni M, Chambon P, Lathe R (1990) hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma. Embo J 9:407–414

    PubMed  CAS  Google Scholar 

  • Tomasetto C, Masson R, Linares JL, Wendling C, Lefebvre O, Chenard MP, Rio MC (2000) pS2/TFF1 interacts directly with the VWFC cysteine-rich domains of mucins. Gastroenterology 118:70–80

    Article  PubMed  CAS  Google Scholar 

  • Williams GR, Wright NA (1997) Trefoil factor family domain peptides. Virchows Arch 431:299–304

    Article  PubMed  CAS  Google Scholar 

  • Wong WM, Poulsom R, Wright N (1999) Trefoil peptides. Gut 44:890–895

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the Grants-in-Aid for Scientific Research 17590488 (to HO) and supported by 17390160 (to TK) from Japan Society for the promotion of Science.

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Authors and Affiliations

  1. Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    H. Ota, M. Hayama & N. Okumura

  2. Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Japan

    M. Momose, K. Matsuda & K. Sano

  3. Department of Laboratory Medicine, School of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Japan

    T. Katsuyama

  4. Department of Surgery, School of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Japan

    F. Maruta

  5. Department of Pathology, Baylor College of Medicine, Houston, TX, USA

    Hala M. T. El-Zimaity

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  1. H. Ota
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  2. M. Hayama
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  3. M. Momose
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  4. Hala M. T. El-Zimaity
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  5. K. Matsuda
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  6. K. Sano
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  7. F. Maruta
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  8. N. Okumura
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  9. T. Katsuyama
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Correspondence to H. Ota.

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Ota, H., Hayama, M., Momose, M. et al. Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa. Histochem Cell Biol 126, 617–625 (2006). https://doi.org/10.1007/s00418-006-0197-y

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  • DOI: https://doi.org/10.1007/s00418-006-0197-y

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