Abstract:
:Skin fibrosis is mainly characterized by excessive collagen deposition. Studies have recently identified a number of flavonoids with variable structures that have the potency of inhibiting collagen synthesis and thus attenuating organ fibrosis. In this study, we found that flavones with 5, 7, 3', 4' hydroxy substitution reduced collagen expression most efficiently. Among those flavones, luteolin, quercetin, and myricetin were selected for follow-up. In vivo, the three compounds ameliorated skin fibrosis and reduced collagen deposition. Further analysis showed the compounds had significant inhibition on the proliferation, activation and contractile ability of dermal fibroblasts in vitro and in vivo. More importantly, we revealed that luteolin, quercetin, and myricetin selectively downregulated the phosphorylation of Smad2/3 in TGF-β/Smads signaling via binding to activin receptor-like kinase 5 (ALK5) and impairing its catalytic activity. We also found flavones with 5, 7, 3', 4' hydroxy substitution showed stronger affinity with ALK5 compared with other flavonoids. Herein, we identified at least in part the underlying molecular basis as well as the critical structures that contribute to the antifibrotic bioactivity of flavones, which might benefit drug design and modification.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Zhang Y,Wang J,Zhou S,Xie Z,Wang C,Gao Y,Zhou J,Zhang X,Li Qdoi
10.1038/s41419-019-1333-7subject
Has Abstractpub_date
2019-02-11 00:00:00pages
124issue
2issn
2041-4889pii
10.1038/s41419-019-1333-7journal_volume
10pub_type
杂志文章abstract::Although Yes-associated protein (YAP) is very important to liver cancer, its nuclear localisation prevents consideration as a promising therapeutic target and a diagnostic biomarker. Recently, we reported that the protumourigenic roles of YAP in liver cancer are indispensable for transcription factor CP2 (TFCP2) in a ...
journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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pub_type: 杂志文章,评审
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pub_type: 已发布勘误
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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