Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact
| Autor: | Dong Shang, Ya Liu, Tian Yang, Hui Ren, Mingwei Chen, Pang Yamei, Jinyuan Wang, Xiaomin Dang |
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| Rok vydání: | 2016 |
| Předmět: |
Lung Diseases
0301 basic medicine Cancer Research Pathology SMAD sirtuin 2 Biochemistry Pulmonary function testing Mice chemistry.chemical_compound Sirtuin 1 Fibrosis Lung transforming growth factor-β1 medicine.diagnostic_test Inhalation Articles respiratory system Silicon Dioxide medicine.anatomical_structure Oncology Molecular Medicine Bronchoalveolar Lavage Fluid medicine.medical_specialty Emodin Silicosis Enzyme-Linked Immunosorbent Assay Collagen Type I Transforming Growth Factor beta1 03 medical and health sciences Genetics medicine Animals Humans Smad3 Protein Molecular Biology business.industry lung fibrosis small mothers against decapentaplegic medicine.disease Actins Disease Models Animal 030104 developmental biology Bronchoalveolar lavage Gene Expression Regulation chemistry Cancer research business |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation‑induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α‑smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor‑β1 (TGF‑β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme‑linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography‑mass spectrometry analysis. The deposition of collagen I and α‑SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF‑β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1‑regulated TGF‑β1/Smad signaling was involved in silica inhalation‑induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling. |
| Databáze: | OpenAIRE |
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