title: Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact.
abstract: 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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Dang
authors.affiliation: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Shang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D004642:Emodin; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics*; D051900:Smad3 Protein / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000199:Actins; D024042:Collagen Type I; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D012822:Silicon Dioxide; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D004642:Emodin