title: Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1-induced EMT in experimental lung fibrosis and clarify its mechanism of action.
  
  
  METHODS
  The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice.
  
  
  RESULTS
  TGF-β1-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1-induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1-induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium.
  
  
  CONCLUSIONS
  Our data demonstrate that ApoA1 inhibits TGF-β1-induced EMT in experimental lung fibrosis.
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Ae Rin
authors.initials: AR
authors.lastname: Baek
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Seo
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: June Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: An Soo
authors.initials: AS
authors.lastname: Jang
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Do Jin
authors.initials: do J
authors.lastname: Kim
authors.affiliation: Department of Pathology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Koh
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Hospital, Seoul, Korea.
authors.forename: Soo Taek
authors.initials: ST
authors.lastname: Uh
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Choon Sik
authors.initials: CS
authors.lastname: Park
keywords: Apolipoprotein A-1; Epithelial-Mesenchymal Transition; Pulmonary Fibrosis; Transforming Growth Factor Beta1