title: D-4F, an apolipoprotein A-I mimetic, inhibits TGF-β1 induced epithelial-mesenchymal transition in human alveolar epithelial cell.
abstract: Emerging evidences support that transforming growth factor β1 (TGF-β1) induced epithelial-mesenchymal transition (EMT) participates in the pathogenesis of pulmonary fibrosis and asthmatic airway remodeling. Recent studies demonstrated that apolipoprotein A-I (Apo A-I) is the only known substance that can resolve established pulmonary fibrotic nodules, and Apo A-I mimetic D-4F (a synthetic polypeptide consisting of 18 amino acids) plays an inhibitory role in murine asthmatic model. However, cellular mechanisms for such therapeutic effects of Apo A-I and D-4F remain to be elucidated. This study evaluated the effects of D-4F on TGF-β1 induced EMT in human type II alveolar epithelial cell line A549. A549 cells treated with 10ng/ml of TGF-β1 manifested distinct EMT, including fibroblastic morphological changes, down-regulation of epithelial marker E-cadherin and up-regulation of mesenchymal marker vimentin. These EMT related changes were all inhibited by D-4F in a concentration dependent manner. Transcriptional investigation demonstrated clearly that D-4F dose-dependently compensated for the reduced E-cadherin mRNA level and the increased vimentin mRNA level in TGF-β1 treated A549 cells. Translational analysis revealed that D-4F significantly reversed the TGF-β1 induced changes of E-cadherin and vimentin levels. These results suggested that D-4F inhibits TGF-β1 induced EMT in human alveolar epithelial cell. Given the functional similarities between D-4F and Apo A-I, it is speculated that D-4F and Apo A-I are able to exert possible anti-fibrotic and anti-asthmatic effects via inhibiting alveolar EMT, and D-4F may possess beneficial clinical potential for patients suffering from pulmonary fibrosis and asthma.
authors: Research Center for Public Health and Preventive Medicine, West China School of Public Health, Sichuan University, Chengdu, 610041, China; Research Center for Occupational Respiratory Diseases, West China School of Public Health, Sichuan University, Chengdu, 610041, China.
authors: Jia
authors: J
authors: You
authors: Department of Environmental and Occupational Medicine, West China School of Public Health, Sichuan University, Chengdu, 610041, China.
authors: Jintao
authors: J
authors: Wang
authors: No. 4 West China Teaching Hospital, Sichuan University, Chengdu, 610041, China.
authors: Linshen
authors: L
authors: Xie
authors: Department of Environmental and Occupational Medicine, West China School of Public Health, Sichuan University, Chengdu, 610041, China.
authors: Chengwen
authors: C
authors: Zhu
authors: Research Center for Public Health and Preventive Medicine, West China School of Public Health, Sichuan University, Chengdu, 610041, China; Research Center for Occupational Respiratory Diseases, West China School of Public Health, Sichuan University, Chengdu, 610041, China. Electronic address: jzx0004@tigermail.auburn.edu.
authors: Jingyuan
authors: J
authors: Xiong
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000473:pathology*; D016632:Apolipoprotein A-I / Q000378:metabolism / Q000494:pharmacology*; D001249:Asthma / Q000473:pathology; D015153:Blotting, Western; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016133:Polymerase Chain Reaction; D011658:Pulmonary Fibrosis / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; C465468:D-4F peptide; D053773:Transforming Growth Factor beta1
keywords: Asthma; D-4F; EMT; Pulmonary fibrosis; TGF-β1