ReferenceID 4368

Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β signaling via targeting HSP90β

Biochem Pharmacol

Idiopathic 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

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Reference Id
4368
Evidence Id
20958
Core Evidence Id
20958
Source Reference Id
2002
Herb2 Reference Id
HBREF002799
Subject Paper Key
HBIN007081_32535102
Pubmed Id
32535102
Doi
10.1016/j.bcp.2020.114097
Paper Title
Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β signaling via targeting HSP90β
Paper Abstract
Idiopathic 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)-beta signaling pathway. In vitro studies indicated that myricetin could dose-dependently suppress TGF-beta1/Smad signaling and attenuate TGF-beta1-induced fibroblast activation and epithelial-mesenchymal transition (EMT). Molecular docking indicated that heat shock protein (HSP) 90beta may be a potential target of myricetin, and MST assay demonstrated that the dissociation constant (Kd) of myricetin and HSP90beta was 331.59 nM. We demonstrated that myricetin interfered with the binding of HSP90beta and TGF-beta receptor II and impeded fibroblast activation and EMT. In conclusion, myricetin impedes TGF-beta1-induced lung fibroblast activation and EMT via targeting HSP90beta and attenuates BLM-induced pulmonary fibrosis in mice.
Journal
Biochem Pharmacol
Publish Year
2020
Experiment Subject
mouse
Experiment Type
Animal & Cell Experiment
Phenotype Related
Idiopathic Pulmonary Fibrosis; Progressive-fibrosing Lung Disease; Pulmonary Fibrosis
Paper Title Cn
Paper Title En
Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β signaling via targeting HSP90β
Bilingual Status
semi_complete