2. Academic Validation
  3. Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin

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

  • Mol Ther. 2023 Oct 4;31(10):3015-3033. doi: 10.1016/j.ymthe.2023.08.017.
Mengjiao Hao 1,  Zhuoji Guan 2,  Zhikang Zhang 3,  Haopeng Ai 3,  Xing Peng 3,  Huihao Zhou 3,  Jun Xu 4,  Qiong Gu 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangdong Key Laboratory of Tea Resources Innovation & Utilization, Guangzhou 510640, China.
  • 2 The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
  • 3 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 4 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: [email protected].
  • 5 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address: [email protected].
PMID: 37641404 DOI: 10.1016/j.ymthe.2023.08.017
Abstract

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-β1-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-β Receptor I recycling by binding to VIM (KD = 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-β/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-β Receptor I recycling. These findings paved the way to develop new targeted therapeutics against PF.

Keywords

TGF-β receptor; TGF-β/Smad; atractylodinol; pulmonary fibrosis; vimentin.

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