Skip to main content

Advertisement

SpringerLink
Log in

Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to characterize pathological lesions of the esophageal epithelial tight junction (TJ) complex in a rat reflux esophagitis (RE) model in a search for a reliable diagnostic indicator.

Methods

Rats underwent an operation to induce RE, with or without rabeprazole treatment (1.0 and 10.0 mg/kg/day). Sham-operated rats served as a control. Fourteen days after the operation, esophagi were isolated from the rats and submitted to double-label confocal immunofluorescence microscopy, and biochemical analyses.

Results

Immunofluorescence microscopy revealed that claudins-1, -3, and -4 were located on the surfaces of epithelial cells in the normal esophagus of the control group, although there were differences in the distribution patterns between claudin-3 and claudins-1 and -4 in the epithelial layer. However, in RE, the immunoreactivity of claudin-3 on the cell surface was decreased, and it appeared instead as a faint granular pattern within the epithelial cytoplasm. Claudin-3 expression in the entire esophageal epithelium was also decreased. The expression and location of claudins-1 and -4 in epithelial cells were basically unaffected in RE. Gastric acid-induced dissociation of claudin-3 elicited instability of the epithelial TJ complex, which was confirmed by sedimentation analysis using centrifugation in a sucrose density gradient. Rabeprazole (10.0 mg/kg/day) attenuated these alterations.

Conclusions

Our data indicate that the dispersion of claudin-3 from esophageal epithelial plasma membranes to cytoplasm and the resulting instability of the TJ complex could be one of the most specific and sensitive indicators for monitoring inflammatory and recovery processes in RE.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Fujimoto K. Review article: prevalence and epidemiology of gastro-oesophageal reflux disease in Japan. Aliment Pharmacol Ther. 2004;20(Suppl 8):5–8.

    Article  PubMed  Google Scholar 

  2. Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44:518–34.

    Article  PubMed  Google Scholar 

  3. Watanabe S, Hojo M, Nagahara A. Metabolic syndrome and gastrointestinal diseases. J Gastroenterol. 2007;42:267–74.

    Article  PubMed  Google Scholar 

  4. Yoshimura M, Nagahara A, Ohtaka K, Shimada Y, Asaoka D, Kurosawa A, et al. Presence of vertebral fractures is highly associated with hiatal hernia and reflux esophagitis in Japanese elderly people. Intern Med. 2008;47:1451–5.

    Article  PubMed  Google Scholar 

  5. Corley DA, Kubo A, Levin TR, Block G, Habel L, Rumore G, et al. Helicobacter pylori and gastroesophageal reflux disease: a case–control study. Helicobacter. 2008;13:352–60.

    Article  PubMed  Google Scholar 

  6. Hongo M, Kinoshita Y, Miwa H, Ashida K. The demographic characteristics and health-related quality of life in a large cohort of reflux esophagitis patients in Japan with reference to the effect of lansoprazole: the REQUEST study. J Gastroenterol. 2008;43:920–7.

    Article  PubMed  Google Scholar 

  7. Henke CJ, Levin TR, Henning JM, Potter LP. Work loss costs due to peptic ulcer disease and gastroesophageal reflux disease in a health maintenance organization. Am J Gastroenterol. 2000;95:788–92.

    Article  PubMed  CAS  Google Scholar 

  8. Richter JE, Castell DO. Gastroesophageal reflux. Pathogenesis, diagnosis, and therapy. Ann Intern Med. 1982;97:93–103.

    PubMed  CAS  Google Scholar 

  9. Orlando RC. Review article: oesophageal mucosal resistance. Aliment Pharmacol Ther. 1998;12:191–7.

    Article  PubMed  CAS  Google Scholar 

  10. Steed E, Balda MS, Matter K. Dynamics and functions of tight junctions. Trends Cell Biol. 2010;20:142–9.

    Article  PubMed  CAS  Google Scholar 

  11. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2:285–93.

    Article  PubMed  CAS  Google Scholar 

  12. Findley M, Koval M. Regulation and roles for claudin-family tight junction proteins. IUBMB Life. 2009;61:431–7.

    Article  PubMed  CAS  Google Scholar 

  13. Staehelin LA. Further observations on the fine structure of freeze-cleaved tight junctions. J Cell Sci. 1973;13:763–86.

    PubMed  CAS  Google Scholar 

  14. Shin K, Fogg VC, Margolis B. Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 2006;22:207–35.

    Article  PubMed  CAS  Google Scholar 

  15. Sonoda N, Furuse M, Sasaki H, Yonemura S, Katahira J, Horiguchi Y, et al. Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: evidence for direct involvement of claudins in tight junction barrier. J Cell Biol. 1999;147:195–204.

    Article  PubMed  Google Scholar 

  16. Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut. 2007;56:61–72.

    Article  PubMed  CAS  Google Scholar 

  17. Bürgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD. Mechanisms of diarrhea in collagenous colitis. Gastroenterology. 2002;123:433–43.

    Article  PubMed  Google Scholar 

  18. Asaoka D, Miwa H, Hirai S, Ohkawa A, Kurosawa A, Kawabe M, et al. Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis. J Gastroenterol. 2005;40:781–90.

    Article  PubMed  Google Scholar 

  19. Omura N, Kashiwagi H, Chen G, Suzuki Y, Yano F, Aoki T. Establishment of surgically induced chronic acid reflux esophagitis in rats. Scand J Gastroenterol. 1999;34:948–53.

    Article  PubMed  CAS  Google Scholar 

  20. Asaoka D, Nagahara A, Oguro M, Mori H, Nakae K, Izumi Y, et al. Establishment of a reflux esophago-laryngitis model in rats. Dig Dis Sci. 2010 [Epub ahead of print].

  21. Tanaka M, Katoh Y, Nakajima Y, Kawashima H. Combination effects of rabeprazole and teprenone on gastric mucosal lesion model induced by indomethacin. Jpn Pharmacol Ther. 1998;26:981–7 (article in Japanese with English abstract).

    Google Scholar 

  22. Koike M, Shibata M, Ohsawa Y, Kametaka S, Waguri S, Kominami E, et al. The expression of tripeptidyl peptidase I in various tissues of rats and mice. Arch Histol Cytol. 2002;65:219–32.

    Article  PubMed  CAS  Google Scholar 

  23. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141:1539–50.

    Article  PubMed  CAS  Google Scholar 

  24. Nusrat A, Parkos C, Verkade P, Foley CS, Liang TW, Innis-Whitehouse W, et al. Tight junctions are membrane microdomains. J Cell Sci. 2000;113(Pt 10):1771–81.

    PubMed  CAS  Google Scholar 

  25. Fujita H, Chiba H, Yokozaki H, Sakai N, Sugimoto K, Wada T, et al. Differential expression and subcellular localization of claudin-7, -8, -12, -13, and -15 along the mouse intestine. J Histochem Cytochem. 2006;54:933–44.

    Article  PubMed  CAS  Google Scholar 

  26. Hashimoto K, Oshima T, Tomita T, Kim Y, Matsumoto T, Joh T, et al. Oxidative stress induces gastric epithelial permeability through claudin-3. Biochem Biophys Res Commun. 2008;376:154–7.

    Article  PubMed  CAS  Google Scholar 

  27. Miwa H, Oshima T, Sakurai J, Tomita T, Matsumoto T, Iizuka S, et al. Experimental oesophagitis in the rat is associated with decreased voluntary movement. Neurogastroenterol Motil. 2009;21:296–303.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Masako Oguro, Daisuke Asaoka, Hiroki Mori, Akihito Nagahara & Sumio Watanabe

  2. Department of Cell Biology and Neuroscience, Juntendo University School of Medicine, Tokyo, Japan

    Masato Koike & Yasuo Uchiyama

  3. Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan

    Takashi Ueno

Authors
  1. Masako Oguro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masato Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takashi Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daisuke Asaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akihito Nagahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuo Uchiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sumio Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sumio Watanabe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oguro, M., Koike, M., Ueno, T. et al. Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease. J Gastroenterol 46, 629–638 (2011). https://doi.org/10.1007/s00535-011-0390-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-011-0390-1

Keywords

Search

Navigation