Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells.
10.4046/trd.2016.79.3.143
- Author:
Ae Rin BAEK
1
;
Ji Min LEE
;
Hyun Jung SEO
;
Jong Sook PARK
;
June Hyuk LEE
;
Sung Woo PARK
;
An Soo JANG
;
Do Jin KIM
;
Eun Suk KOH
;
Soo Taek UH
;
Yong Hoon KIM
;
Choon Sik PARK
Author Information
1. Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea. swpark@schmc.ac.kr
- Publication Type:Original Article
- Keywords:
Apolipoprotein A-1;
Transforming Growth Factor Beta1;
Epithelial-Mesenchymal Transition;
Pulmonary Fibrosis
- MeSH:
Actins;
Animals;
Apolipoprotein A-I*;
Apolipoproteins*;
Cadherins;
Epithelial Cells*;
Epithelial-Mesenchymal Transition;
Epithelium;
Extracellular Matrix;
Fibroblasts;
Fibrosis;
Idiopathic Pulmonary Fibrosis;
Lung;
Lung Diseases;
Mice;
Mice, Transgenic;
Myofibroblasts;
Phenotype;
Phosphorylation;
Protein Kinases;
Pulmonary Fibrosis;
Transforming Growth Factor beta1;
Transforming Growth Factors
- From:Tuberculosis and Respiratory Diseases
2016;79(3):143-152
- CountryRepublic of Korea
- Language:English
-
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. CONCLUSION: Our data demonstrate that ApoA1 inhibits TGF-β1-induced EMT in experimental lung fibrosis.
