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Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet.
Dig Liver Dis. 2004 May; 36(5):337-41.DL

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.

Authors+Show Affiliations

Department of Surgical and Gastroenterological Sciences, Section of Gastroenterology, University of Padua, Via Giustiniani 2, 35128 Padua, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15191203

Citation

Pizzuti, D, et al. "Transcriptional Downregulation of Tight Junction Protein ZO-1 in Active Coeliac Disease Is Reversed After a Gluten-free Diet." Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, vol. 36, no. 5, 2004, pp. 337-41.
Pizzuti D, Bortolami M, Mazzon E, et al. Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. Dig Liver Dis. 2004;36(5):337-41.
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 : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 36(5), 337-41.
Pizzuti D, et al. Transcriptional Downregulation of Tight Junction Protein ZO-1 in Active Coeliac Disease Is Reversed After a Gluten-free Diet. Dig Liver Dis. 2004;36(5):337-41. PubMed PMID: 15191203.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. AU - Pizzuti,D, AU - Bortolami,M, AU - Mazzon,E, AU - Buda,A, AU - Guariso,G, AU - D'Odorico,A, AU - Chiarelli,S, AU - D'Incà,R, AU - De Lazzari,F, AU - Martines,D, PY - 2004/6/12/pubmed PY - 2004/9/24/medline PY - 2004/6/12/entrez SP - 337 EP - 41 JF - Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver JO - Dig Liver Dis VL - 36 IS - 5 N2 - UNLABELLED: 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. SN - 1590-8658 UR - https://www.unboundmedicine.com/medline/citation/15191203/Transcriptional_downregulation_of_tight_junction_protein_ZO_1_in_active_coeliac_disease_is_reversed_after_a_gluten_free_diet_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1590-8658(04)00059-3 DB - PRIME DP - Unbound Medicine ER -