Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin

doi:10.1016/j.ymthe.2023.08.017

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	Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin
	Hao,Mengjiao; Guan,Zhuoji; Zhang,Zhikang; Ai,Haopeng; Peng,Xing; Zhou,Huihao; Xu,Jun; Gu,Qiong
	2023
发表期刊	MOLECULAR THERAPY
ISSN	1525-0024
卷号	31 期号:10 页码:3015-3033
摘要	Pirfenidone and nintedanib are only anti-pulmonary fibrosis (PF) drugs approved by the FDA. However, they are not target specific, and unable to modify the disease status. Therefore, it is still desirable to discover more effective agents against PF. Vimentin (VIM) plays key roles in tissue regeneration and wound healing, but its molecular mechanism remains unknown. In this work, we demonstrated that atractylodinol (ATD) significantly inhibits TGF-beta 1-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transition in vitro. ATD also reduces bleomycin-induced lung injury and fibrosis in mice models. Mechanistically, ATD inhibited TGF-beta receptor I recycling by binding to VIM (K-D = 454 nM) and inducing the formation of filamentous aggregates. In conclusion, we proved that ATD (derived from Atractylodes lancea) modified PF by targeting VIM and inhibiting the TGF-beta/Smad signaling pathway. Therefore, VIM is a druggable target and ATD is a proper drug candidate against PF. We prove a novel VIM function that TGF-beta-receptor I recycling. These findings paved the way to develop new targeted therapeutics against PF.
关键词	INTERMEDIATE-FILAMENT PROTEIN MECHANISMS PATHWAYS ADHESION IDENTIFICATION SMAD
DOI	10.1016/j.ymthe.2023.08.017
收录类别	SCI
WOS记录号	WOS:001088359100001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75535
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Hao,Mengjiao,Guan,Zhuoji,Zhang,Zhikang,et al. Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin[J]. MOLECULAR THERAPY,2023,31(10):3015-3033.
APA	Hao,Mengjiao.,Guan,Zhuoji.,Zhang,Zhikang.,Ai,Haopeng.,Peng,Xing.,...&Gu,Qiong.(2023).Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin.MOLECULAR THERAPY,31(10),3015-3033.
MLA	Hao,Mengjiao,et al."Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin".MOLECULAR THERAPY 31.10(2023):3015-3033.

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