title: Plakoglobin expression in fibroblasts and its role in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is an interstitial fibrotic lung disease of unknown origin and without effective therapy characterized by deposition of extracellular matrix by activated fibroblasts in the lung. Fibroblast activation in IPF is associated with Wnt/β-catenin signaling, but little is known about the role of the β-catenin-homologous desmosomal protein, plakoglobin (PG), in IPF. The objective of this study was to assess the functional role of PG in human lung fibroblasts in IPF.
  
  
  METHODS
  Human lung fibroblasts from normal or IPF patients were transfected with siRNA targeting PG and used to assess cellular adhesion to a fibronectin substrate, apoptosis and proliferation. Statistical analysis was performed using Student's t-test with Mann-Whitney post-hoc analyses and results were considered significant when p < 0.05.
  
  
  RESULTS
  We found that IPF lung fibroblasts expressed less PG protein than control fibroblasts, but that characteristic fibroblast phenotypes (adhesion, proliferation, and apoptosis) were not controlled by PG expression. Consistent with this, normal fibroblasts in which PG was silenced displayed no change in functional phenotype.
  
  
  CONCLUSIONS
  We conclude that diminished PG levels in IPF lung fibroblasts do not directly affect certain phenotypic behaviors. Further study is needed to identify the functional consequences of decreased PG in these cells.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109-5642, USA. saboeck@med.umich.edu.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Matthes
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109-5642, USA. tlarouere@gmail.com.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: LaRouere
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109-5642, USA. jchorow@med.umich.edu.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Horowitz
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109-5642, USA. docew@med.umich.edu.
authors.forename: Eric S
authors.initials: ES
authors.lastname: White
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D051180:Desmoplakins / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051185:gamma Catenin
chemical_list: D051180:Desmoplakins; D005353:Fibronectins; C495292:JUP protein, human; D012333:RNA, Messenger; D051185:gamma Catenin