JOURNAL ARTICLE

Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells

Ae Rin Baek, 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
Tuberculosis and Respiratory Diseases 2016, 79 (3): 143-52
27433174

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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