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KMID : 0383820160790030143
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Tuberculosis and Respiratory Diseases
2016 Volume.79 No. 3 p.143 ~ p.152
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Apolipoprotein A1 Inhibits TGF-β1?Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells
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Baek Ae-Rin
Lee Ji-Min
Seo Hyun-Jung
Park Jong-Sook
Lee June-Hyuk
Park Sung-Woo
Jang An-Soo
Kim Do-Jin
Koh Eun-Suk
Uh Soo-Taek
Kim Yong-Hoon
Park Choon-Sik
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Abstract
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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.
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KEYWORD
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Apolipoprotein A-1, Transforming Growth Factor Beta1, Epithelial-Mesenchymal Transition, Pulmonary Fibrosis
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