title: Roles of p38 MAPK and JNK in TGF-β1-induced human alveolar epithelial to mesenchymal transition.
abstract: OBJECTIVE
  Idiopathic pulmonary fibrosis (IPF) is associated with significant morbidity and mortality despite aggressive therapy. The aim of the present study is to investigate the roles of p38 MAPK and JNK in TGF-β1-induced human alveolar epithelial to mesenchymal transition (EMT), which could be a possible mechanism of IPF.
  
  
  METHODS
  A549 cells were treated with TGF-β1 (3 ng/mL) for 48 h to induce EMT. The expression of mesenchymal phenotypic markers including desmin, α-smooth muscle actin (α-SMA) and vimentin, and expression of epithelial phenotypic markers including E-cadherin, zonula occludens-1 (ZO-1) and aquaporin-5 (AQP5) were detected by Western blot. The roles of p38 MAPK and JNK in TGF-β1-mediated EMT were investigated using gene silencing and inhibitor SB-203580 and SP-600125.
  
  
  RESULTS
  The data showed that TGF-β1 induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT. The process of EMT was accompanied by morphological alteration and expression of the myofibroblast marker desmin, α-SMA and vimentin, concomitant with a downregulation of the epithelial cell marker E-cadherin, ZO-1 and AQP5. TGF-β1-induced EMT occurred through phosphorylation of p38 MAPK and JNK and was inhibited by inhibitor SB-203580 and SP-600125 and gene silencing.
  
  
  CONCLUSIONS
  TGF-β1 induces A549 alveolar epithelial cells (AECs) to undergo EMT partially via p38 MAPK and JNK activation and supports the concept of EMT in lung epithelial cells.
authors: Renmin Hospital of Wuhan University, Wuhan, China. chenhaihua413@gmail.com
authors: Hai-hua
authors: HH
authors: Chen
authors: Xian-long
authors: XL
authors: Zhou
authors: Yu-lu
authors: YL
authors: Shi
authors: Jiong
authors: J
authors: Yang
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000502:physiology*; D000873:Anthracenes / Q000494:pharmacology; D051402:Aquaporin 5 / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007093:Imidazoles; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation; D011725:Pyridines; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D051402:Aquaporin 5; D015820:Cadherins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D053773:Transforming Growth Factor beta1; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580