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

文献类型： 外文期刊

第一作者： Hao, Mengjiao

作者： Hao, Mengjiao;Zhang, Zhikang;Ai, Haopeng;Peng, Xing;Zhou, Huihao;Xu, Jun;Gu, Qiong;Guan, Zhuoji;Hao, Mengjiao;Gu, Qiong

作者机构：

期刊名称：MOLECULAR THERAPY （ 影响因子：12.4； 五年影响因子：12.6 ）

ISSN： 1525-0016

年卷期： 2023 年 31 卷 10 期

页码：

收录情况： SCI

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.

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