Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling
Silicosis is a severe progressive lung disease without effective treatment methods. Previous evidence has demonstrated that endothelial cell to mesenchymal transition (EndoMT) plays an essential role in pulmonary fibrosis, and pulmonary fibrosis is associated with dysregulation of autophagy, while t...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S014765132200940X |
| _version_ | 1811258954974494720 |
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| author | Ning Li Zhang Lin Qiang Zhou Meiyu Chang Yongheng Wang Yi Guan Haibin Li Yingzheng Zhao Nan Liu Yulan Jin Sanqiao Yao |
| author_facet | Ning Li Zhang Lin Qiang Zhou Meiyu Chang Yongheng Wang Yi Guan Haibin Li Yingzheng Zhao Nan Liu Yulan Jin Sanqiao Yao |
| author_sort | Ning Li |
| collection | DOAJ |
| description | Silicosis is a severe progressive lung disease without effective treatment methods. Previous evidence has demonstrated that endothelial cell to mesenchymal transition (EndoMT) plays an essential role in pulmonary fibrosis, and pulmonary fibrosis is associated with dysregulation of autophagy, while the relationship between autophagy and EndoMT has not yet been adequately studied. Herein, we established a mouse model of silicosis, and we found that the pharmacological induction of the AMPK/mTOR-dependent pathway using 100 mg/kg Metformin (Met) enhanced autophagy in vivo, and results of the Western blot showed that autophagy-related proteins, LC3 II/I ratio, and Beclin-1 increased while p62 decreased. In addition, Met treatment attenuated silica-induced pulmonary inflammation and decreased collagen deposition by suppressing EndoMT, and the proliferation of human umbilical vein endothelial cells (HUVECs) was also inhibited. Notably, the tube forming assay showed that Met also protected the vascular endothelial cells from silica-induced morphological damage. In conclusion, Met can alleviate inflammatory response and collagen deposition in the process of pulmonary fibrosis induced by silica via suppressing EndoMT through the AMPK/mTOR signaling pathway. |
| first_indexed | 2024-04-12T18:23:20Z |
| format | Article |
| id | doaj.art-3445d1127f694fbc9dc26d1f656a22d0 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-12T18:23:20Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-3445d1127f694fbc9dc26d1f656a22d02022-12-22T03:21:21ZengElsevierEcotoxicology and Environmental Safety0147-65132022-10-01245114100Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signalingNing Li0Zhang Lin1Qiang Zhou2Meiyu Chang3Yongheng Wang4Yi Guan5Haibin Li6Yingzheng Zhao7Nan Liu8Yulan Jin9Sanqiao Yao10School of Public Health, North China University of Science of Technology, Tangshan 062310, China; School of Public Health, Xinxiang Medical University, Xinxiang 453003, ChinaClinical Medical Research Center for Women and Children Diseases, Maternal and Child Care Hospital of Shandong Province, Shandong University, Jinan 250001, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, ChinaSchool of Public Health, Xinxiang Medical University, Xinxiang 453003, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, ChinaSchool of Public Health, North China University of Science of Technology, Tangshan 062310, China; School of Public Health, Xinxiang Medical University, Xinxiang 453003, China; Correspondence to: School of Public Health, North China University of Science of Technology, 063210 Tangshan, China.Silicosis is a severe progressive lung disease without effective treatment methods. Previous evidence has demonstrated that endothelial cell to mesenchymal transition (EndoMT) plays an essential role in pulmonary fibrosis, and pulmonary fibrosis is associated with dysregulation of autophagy, while the relationship between autophagy and EndoMT has not yet been adequately studied. Herein, we established a mouse model of silicosis, and we found that the pharmacological induction of the AMPK/mTOR-dependent pathway using 100 mg/kg Metformin (Met) enhanced autophagy in vivo, and results of the Western blot showed that autophagy-related proteins, LC3 II/I ratio, and Beclin-1 increased while p62 decreased. In addition, Met treatment attenuated silica-induced pulmonary inflammation and decreased collagen deposition by suppressing EndoMT, and the proliferation of human umbilical vein endothelial cells (HUVECs) was also inhibited. Notably, the tube forming assay showed that Met also protected the vascular endothelial cells from silica-induced morphological damage. In conclusion, Met can alleviate inflammatory response and collagen deposition in the process of pulmonary fibrosis induced by silica via suppressing EndoMT through the AMPK/mTOR signaling pathway.http://www.sciencedirect.com/science/article/pii/S014765132200940XSilicosisAutophagyEndothelial cell to mesenchymal transitionMetformin |
| spellingShingle | Ning Li Zhang Lin Qiang Zhou Meiyu Chang Yongheng Wang Yi Guan Haibin Li Yingzheng Zhao Nan Liu Yulan Jin Sanqiao Yao Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling Ecotoxicology and Environmental Safety Silicosis Autophagy Endothelial cell to mesenchymal transition Metformin |
| title | Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling |
| title_full | Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling |
| title_fullStr | Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling |
| title_full_unstemmed | Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling |
| title_short | Metformin alleviates crystalline silica-induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling |
| title_sort | metformin alleviates crystalline silica induced pulmonary fibrosis by remodeling endothelial cells to mesenchymal transition via autophagy signaling |
| topic | Silicosis Autophagy Endothelial cell to mesenchymal transition Metformin |
| url | http://www.sciencedirect.com/science/article/pii/S014765132200940X |
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