title: Alteration of tight junction gene expression in celiac disease.
abstract: 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.
authors.affiliation: *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.
authors.forename: Amaia
authors.initials: A
authors.lastname: Jauregi-Miguel
authors.forename: Nora
authors.initials: N
authors.lastname: Fernandez-Jimenez
authors.forename: Iñaki
authors.initials: I
authors.lastname: Irastorza
authors.forename: Leticia
authors.initials: L
authors.lastname: Plaza-Izurieta
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Vitoria
authors.forename: Jose Ramon
authors.initials: JR
authors.lastname: Bilbao
mesh_terms: D002446:Celiac Disease / Q000178:diet therapy / Q000235:genetics*; D016764:Cell Polarity; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D055050:Diet, Gluten-Free; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D010539:Permeability; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions
chemical_list: C525688:PPP2R3A protein, human; D054648:Protein Phosphatase 2