title: Modulation of epithelial tight junctions by TGF-beta 3 in cultured oral epithelial cells.
abstract: BACKGROUND
  Previous studies have indicated that transforming growth factor beta 3 (TGF-β3) was strongly expressed both in the gingival epithelium and the poorly structured pocket epithelium.
  
  
  METHODS
  A comprehensive analysis of the profile of tight junction proteins was carried out by quantitative real-time RT-PCR, Western blot and paracellular permeability assays.
  
  
  RESULTS
  Active TGF-β3 protein added to monolayers of cultured oral epithelial cells initially reduced the permeability to dextran (10 kDa), followed by an increase in permeability. Three hours after the addition of TGF-β3, expression of genes encoding tight junction components was selectively up- or down-regulated. In addition, up- or down-regulation of expression of several tight junction associated proteins was observed, although the protein changes did not parallel changes in gene expression. To confirm that TGF-β3 plays a role in epithelial barrier function, a selective Src family kinase inhibitor saracatinib (AZD0530) was added to cells treated with active TGF-β3. Tight junction proteins claudins-2, -20 and ZO-2 were significantly decreased, but claudin-4 and -18 were significantly increased.
  
  
  CONCLUSIONS
  These results suggest that TGF-β3 is involved in the modulation of epithelial barrier function by regulating assembly of tight junctions.
authors.affiliation: Institute of Dental Research, Westmead Millennium Institute and Westmead Centre for Oral Health, Westmead Hospital, Westmead, New South Wales. ping_ye@wmi.usyd.edu.au
authors.forename: P
authors.initials: P
authors.lastname: Ye
mesh_terms: D052117:Benzodioxoles / Q000494:pharmacology; D000081247:CSK Tyrosine-Protein Kinase; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D057167:Claudins / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology; D020869:Gene Expression Profiling; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D062793:Occludin; D010514:Periodontal Pocket / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*; D053782:Transforming Growth Factor beta3 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D019061:src-Family Kinases
chemical_list: D052117:Benzodioxoles; D015815:Cell Adhesion Molecules; D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011994:Recombinant Proteins; D053782:Transforming Growth Factor beta3; C515233:saracatinib; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human