Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contribut...
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/20/11152 |
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| author | Kai-Wei Chang Xiang Zhang Shih-Chao Lin Yu-Chao Lin Chia-Hsiang Li Ivan Akhrymuk Sheng-Hao Lin Chi-Chien Lin |
| author_facet | Kai-Wei Chang Xiang Zhang Shih-Chao Lin Yu-Chao Lin Chia-Hsiang Li Ivan Akhrymuk Sheng-Hao Lin Chi-Chien Lin |
| author_sort | Kai-Wei Chang |
| collection | DOAJ |
| description | Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice. |
| first_indexed | 2024-03-10T06:29:51Z |
| format | Article |
| id | doaj.art-719e6204cb1648cf9a6fc17c86941541 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:29:51Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-719e6204cb1648cf9a6fc17c869415412023-11-22T18:34:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201115210.3390/ijms222011152Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in MiceKai-Wei Chang0Xiang Zhang1Shih-Chao Lin2Yu-Chao Lin3Chia-Hsiang Li4Ivan Akhrymuk5Sheng-Hao Lin6Chi-Chien Lin7Department of Chest Surgery, Tung’s Taichung MetroHarbor Hospital, Taichung 435, TaiwanDepartment of Molecular Medicine and Surgery, Karolinska Institute, 17176 Stockholm, SwedenBachelor Degree Program in Marine Biotechnology, College of Life Sciences, National Taiwan Ocean University, Keelung 202, TaiwanGraduate Institute of Biomedical Science, China Medical University, Taichung 404, TaiwanGraduate Institute of Biomedical Science, China Medical University, Taichung 404, TaiwanDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USADivision of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, TaiwanInstitute of Biomedical Science, National Chung-Hsing University, Taichung 402, TaiwanIdiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.https://www.mdpi.com/1422-0067/22/20/11152idiopathic pulmonary fibrosistransforming growth factor-beta 1epithelial-mesenchymal transitionatractylodinSmad2/3MAPK |
| spellingShingle | Kai-Wei Chang Xiang Zhang Shih-Chao Lin Yu-Chao Lin Chia-Hsiang Li Ivan Akhrymuk Sheng-Hao Lin Chi-Chien Lin Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice International Journal of Molecular Sciences idiopathic pulmonary fibrosis transforming growth factor-beta 1 epithelial-mesenchymal transition atractylodin Smad2/3 MAPK |
| title | Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_full | Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_fullStr | Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_full_unstemmed | Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_short | Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_sort | atractylodin suppresses tgf β mediated epithelial mesenchymal transition in alveolar epithelial cells and attenuates bleomycin induced pulmonary fibrosis in mice |
| topic | idiopathic pulmonary fibrosis transforming growth factor-beta 1 epithelial-mesenchymal transition atractylodin Smad2/3 MAPK |
| url | https://www.mdpi.com/1422-0067/22/20/11152 |
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