Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet

D. Pizzuti, M. Bortolami, E. Mazzon, A. Buda, G. Guariso, A. D'Odorico, S. Chiarelli, R. D'Incà, F. De Lazzari, D. Martines

Research output: Contribution to journalArticle

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Abstract

Coeliac disease is an autoimmune enteropathy characterized by an enhanced permeability of the intestinal epithelial barrier. In epithelial cells paracellular permeability is regulated by intercellular tight junction. The cytoplasmic protein ZO-1 interacts directly with F-actin and plays a pivotal role in the structural and functional organization of tight junction. Aim. The aim of this study was to investigate the expression and localization of ZO-1 in the intestinal mucosa of coeliac patients. Patients and methods. Twenty patients with active coeliac disease, seven of whom underwent a repeat biopsy following a gluten-free diet and 27 control subjects, were studied. In all subjects, three biopsies were obtained from distal duodenum during upper gastrointestinal endoscopy. ZO-1 protein localization and levels were detected by immunofluorescence followed by confocal microscopy analysis and immunoblotting. ZO-1 mRNA expression was assessed by RT-PCR. F-actin distribution was also investigated. Results. In patients with active coeliac disease, both ZO-1 protein levels and mRNA were clearly reduced. Cytoskeletal organization was disrupted with F-actin staining concentrated at the subcortical and basal surface regions. Abnormalities in ZO-1 expression and actin organization were reversed after a gluten-free diet. Conclusions. In active coeliac disease, ZO-1 protein expression is downregulated at the transcriptional level in association with F-actin redistribution. These changes are completely reversed after a gluten-free diet and could contribute to the increased intestinal paracellular permeability observed in this disorder.

Original languageEnglish
Pages (from-to)337-341
Number of pages5
JournalDigestive and Liver Disease
Volume36
Issue number5
DOIs
Publication statusPublished - May 2004

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Zonula Occludens-1 Protein
Gluten-Free Diet
Celiac Disease
Actins
Down-Regulation
Permeability
Tight Junctions
Proteins
Biopsy
Messenger RNA
Gastrointestinal Endoscopy
Intercellular Junctions
Intestinal Mucosa
Duodenum
Immunoblotting
Confocal Microscopy
Abdomen
Fluorescent Antibody Technique
Epithelial Cells
Staining and Labeling

Keywords

  • Coeliac disease
  • Gluten-free diet
  • Tight junction

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. / Pizzuti, D.; Bortolami, M.; Mazzon, E.; Buda, A.; Guariso, G.; D'Odorico, A.; Chiarelli, S.; D'Incà, R.; De Lazzari, F.; Martines, D.

In: Digestive and Liver Disease, Vol. 36, No. 5, 05.2004, p. 337-341.

Research output: Contribution to journalArticle

Pizzuti, D, Bortolami, M, Mazzon, E, Buda, A, Guariso, G, D'Odorico, A, Chiarelli, S, D'Incà, R, De Lazzari, F & Martines, D 2004, 'Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet', Digestive and Liver Disease, vol. 36, no. 5, pp. 337-341. https://doi.org/10.1016/j.dld.2004.01.013
Pizzuti, D. ; Bortolami, M. ; Mazzon, E. ; Buda, A. ; Guariso, G. ; D'Odorico, A. ; Chiarelli, S. ; D'Incà, R. ; De Lazzari, F. ; Martines, D. / Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. In: Digestive and Liver Disease. 2004 ; Vol. 36, No. 5. pp. 337-341.
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AU - Buda, A.

AU - Guariso, G.

AU - D'Odorico, A.

AU - Chiarelli, S.

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AU - De Lazzari, F.

AU - Martines, D.

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