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Biochemical pharmacology · Aug 2020
Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β signaling via targeting HSP90β.
- Xiaohe Li, Haiyan Yu, Lu Liang, Zhun Bi, Yanhua Wang, Shaoyan Gao, Mukuo Wang, Hailong Li, Yang Miao, Ruxia Deng, Ling Ma, Jiaoyan Luan, Shuangling Li, Menghan Liu, Jianping Lin, Honggang Zhou, and Cheng Yang.
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China; Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, People's Republic of China.
- Biochem. Pharmacol. 2020 Aug 1; 178: 114097.
AbstractIdiopathic pulmonary fibrosis is a progressive-fibrosing lung disease with high mortality and limited therapy, which characterized by myofibroblasts proliferation and extracellular matrix deposition. Myricetin, a natural flavonoid, has been shown to possess a variety of biological characteristics including anti-inflammatory and anti-tumor. In this study we explored the potential effect and mechanisms of myricetin on pulmonary fibrosis in vivo and vitro. The in vivo studies showed that myricetin effectively alleviated bleomycin (BLM)-induced pulmonary fibrosis. KEGG analysis of RNA-seq data indicated that myricetin could regulate the transforming growth factor (TGF)-β signaling pathway. In vitro studies indicated that myricetin could dose-dependently suppress TGF-β1/Smad signaling and attenuate TGF-β1-induced fibroblast activation and epithelial-mesenchymal transition (EMT). Molecular docking indicated that heat shock protein (HSP) 90β may be a potential target of myricetin, and MST assay demonstrated that the dissociation constant (Kd) of myricetin and HSP90β was 331.59 nM. We demonstrated that myricetin interfered with the binding of HSP90β and TGF-β receptor II and impeded fibroblast activation and EMT. In conclusion, myricetin impedes TGF-β1-induced lung fibroblast activation and EMT via targeting HSP90β and attenuates BLM-induced pulmonary fibrosis in mice.Copyright © 2020 Elsevier Inc. All rights reserved.
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