Objective: The aim of the present study was to characterize the deregulation of epithelial tight junction genes and investigate its reversibility on removal of dietary gluten in small intestinal mucosa in celiac disease (CD).
Methods: The expression levels of 23 genes related to tight junctions were studied in biopsies from 16 patients with active CD and compared with biopsies from the same patients taken after 2 years on gluten-free diet (GFD) and with 16 non-CD controls.
Results: Nine genes showed altered expression levels in patients with active disease (CLDN2, PARD6A, ZAK, SYMPK, MYH14, and ACTB were upregulated, whereas MAGI1, TJP1, and PPP2R3A were downregulated). Alterations were reversible after 2 years on treatment, except for PPP2R3A, implicated in the negative control of cell growth and division. At the biological network level, important dysfunctions in several processes within the pathway were observed, including intestinal permeability, apicobasal polarity, and cell proliferation.
Conclusions: Our work confirms the involvement of tight junction genes related to permeability, polarity, and cell proliferation in the epithelial destruction observed in CD. Coexpression patterns of several genes support the idea of a common regulatory mechanism that seems to be altered in active CD. In general, GFD normalization confirms the reversibility of the process, except for the constitutive downregulation of PPP2R3A suggestive of a genetic implication. Further studies in proteins and cells or tissues are necessary to confirm these findings.
*Immunogenetics Research Laboratory, Department of Genetics, Physical Anthropology and Animal Physiology, BioCruces Research Institute, University of the Basque Country UPV/EHU, Leioa
†Department of Pediatrics, Cruces University Hospital, University of the Basque Country UPV/EHU, Barakaldo, Spain.
Address correspondence and reprint requests to Jose Ramon Bilbao, PhD, Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country-UPV/EHU, Bizkaiko Campusa, Leioa 48940, Spain (e-mail: email@example.com).
Received 6 February, 2014
Accepted 6 February, 2014
Supplemental digital content is available for the present article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of the present article on the journal's Web site (www.jpgn.org).
The present work was partially funded by research project grants from the Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness (PI10/0310) and from the Basque Department of Industry (SAIO-PE08BF03) to JRB. NF-J and LP-I are predoctoral fellows supported by FPI grants from the Basque Department of Education, Universities and Research (BIF-2009-099 and BIF-2010-189, respectively).
The authors report no conflicts of interest.