title: EMT and interstitial lung disease:  a mysterious relationship.
abstract: OBJECTIVE
  Pathogenesis of interstitial lung diseases (ILD) has largely been investigated in the context of the most frequent ILD, idiopathic pulmonary fibrosis (IPF). We review studies of epithelial-to-mesenchymal transition (EMT) and discuss its potential contribution to collagen-producing (myo)fibroblasts in IPF.
  
  
  RESULTS
  Endoplasmic reticulum (ER) stress leading to epithelial apoptosis has been reported as a potential etiologic factor in fibrosis. Recent studies further suggest EMT as a link between ER stress and fibrosis. Combinatorial interactions among Smad3, β-catenin and other transcriptional co-activators at the α-smooth muscle actin (α-SMA) promoter provide direct evidence for crosstalk between transforming growth factor-β (TGFβ) and β-catenin pathways during EMT. Lineage tracing yielded conflicting results, with two recent studies supporting and one opposing a role for EMT in lung fibrosis.
  
  
  CONCLUSIONS
  Advances have been made in elucidating causes and mechanisms of EMT, potentially leading to new treatment options, although contributions of EMT to lung fibrosis in vivo remain controversial. In addition to EMT providing a direct source of (myo)fibroblasts, expression of mesenchymal markers may reflect epithelial injury, in which case inhibition of EMT might be deleterious. EMT-derived cells may also contribute to aberrant epithelial-mesenchymal crosstalk that promotes fibrogenesis.
authors.affiliation: Will Rogers Institute Pulmonary Research Center, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kage
authors.forename: Zea
authors.initials: Z
authors.lastname: Borok
mesh_terms: D003094:Collagen / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D008168:Lung / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000473:pathology* / Q000503:physiopathology*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology
chemical_list: D003094:Collagen