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D-4F, an apolipoprotein A-I mimetic, inhibits TGF-β1 induced epithelial-mesenchymal transition in human alveolar epithelial cell
- Source :
- Experimental and Toxicologic Pathology. 68:533-541
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Apolipoprotein B
Pulmonary Fibrosis
Blotting, Western
Vimentin
030204 cardiovascular system & hematology
Biology
Toxicology
Polymerase Chain Reaction
Cell Line
Pathology and Forensic Medicine
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Pulmonary fibrosis
medicine
Humans
Epithelial–mesenchymal transition
A549 cell
Apolipoprotein A-I
Mesenchymal stem cell
Cell Biology
General Medicine
medicine.disease
Asthma
030104 developmental biology
Alveolar Epithelial Cells
Asthmatic Airway Remodeling
Cancer research
biology.protein
Transforming growth factor
Subjects
Details
- ISSN :
- 09402993
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Experimental and Toxicologic Pathology
- Accession number :
- edsair.doi.dedup.....0e73bc94d5de0d889c52cf24adb7e544