Platycodin D2 Targets Vimentin to Suppress Fibroblast-Myofibroblast Transition: A Novel Therapeutic Strategy Against Pulmonary Fibrosis
- 1School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
Abstract
Background Pulmonary fibrosis is a progressive lung disease characterized by excessive extracellular matrix deposition and irreversible decline in lung function with limited effective therapeutic targets. Vimentin, a type III intermediate filament protein, plays a critical role in fibroblast activation and fibrogenesis, representing a promising drug target. Methods Novel vimentin ligands were screened via virtual screening. SPR assay verified compound-vimentin binding affinity. CETSA and CD spectroscopy analyzed protein structural changes after compound binding. In vitro FMT model and in vivo bleomycin-induced pulmonary fibrosis model were used to assess antifibrotic effects, and mutagenesis assays identified key binding amino acid residues. Results Platycodin D2 (PD2) from Platycodon grandiflorus was identified as a novel high-affinity vimentin ligand (Kd = 392.8 nM). PD2 binds vimentin directly, alters its secondary structure and induces insoluble aggregation. It effectively inhibits TGF-{beta}1-induced FMT in vitro and mitigates bleomycin-induced pulmonary fibrosis in vivo, reducing collagen deposition and improving animal survival. Critically, mutagenesis validation confirmed that key residues (Glu138 in chain A, Glu132 and Glu143 in chain B, as well as Glu50 and Arg54 in chain C) are essential for this interaction. Conclusions Our findings establish PD2 as a novel pharmacological inducer of aberrant vimentin aggregation, presenting a distinct target-driven strategy for antifibrotic drug development.
Related
- Delayed Tagging of ED-A Fibronectin-Mimetic Peptide in an RGD-Decorated Synthetic Matrix Induces Fibroblast-to-Myofibroblast Transition
- Loss of PKN2 drives fibroblast reprogramming and extracellular matrix remodelling in pulmonary fibrosis
- CD47 fuels intestinal fibrosis by inducing fibroblast phagocytic evasion and represents a therapeutic target
- Integrating multi-omics and machine learning to reveal IL1R2-driven macrophage-fibroblast spatial interactions in polycyclic aromatic hydrocarbon-induced pulmonary fibrosis
- Sobetirome, a thyroid hormone receptor beta agonist, is a potential therapeutic agent for pulmonary fibrosis
BibTeX
@misc{lang2026platycodin,
title = {{Platycodin D2 Targets Vimentin to Suppress Fibroblast-Myofibroblast Transition: A Novel Therapeutic Strategy Against Pulmonary Fibrosis}},
author = {X. Lang and Z. Ma and C. Yao and X. Miao and Y. Kao and W. Wang and S. Sun},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.763586},
url = {https://www.biorxiv.org/content/10.64898/2026.11.03.763586v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Platycodin D2 Targets Vimentin to Suppress Fibroblast-Myofibroblast Transition: A Novel Therapeutic Strategy Against Pulmonary Fibrosis
AU - X. Lang
AU - Z. Ma
AU - C. Yao
AU - X. Miao
AU - Y. Kao
AU - W. Wang
AU - S. Sun
PY - 2026
DA - 2026/11/03
PB - bioRxiv
DO - 10.64898/2026.11.03.763586
UR - https://www.biorxiv.org/content/10.64898/2026.11.03.763586v1
AB - Background Pulmonary fibrosis is a progressive lung disease characterized by excessive extracellular matrix deposition and irreversible decline in lung function with limited effective therapeutic targets. Vimentin, a type III intermediate filament protein, plays a critical role in fibroblast activation and fibrogenesis, representing a promising drug target. Methods Novel vimentin ligands were screened via virtual screening. SPR assay verified compound-vimentin binding affinity. CETSA and CD spectroscopy analyzed protein structural changes after compound binding. In vitro FMT model and in vivo bleomycin-induced pulmonary fibrosis model were used to assess antifibrotic effects, and mutagenesis assays identified key binding amino acid residues. Results Platycodin D2 (PD2) from Platycodon grandiflorus was identified as a novel high-affinity vimentin ligand (Kd = 392.8 nM). PD2 binds vimentin directly, alters its secondary structure and induces insoluble aggregation. It effectively inhibits TGF-{beta}1-induced FMT in vitro and mitigates bleomycin-induced pulmonary fibrosis in vivo, reducing collagen deposition and improving animal survival. Critically, mutagenesis validation confirmed that key residues (Glu138 in chain A, Glu132 and Glu143 in chain B, as well as Glu50 and Arg54 in chain C) are essential for this interaction. Conclusions Our findings establish PD2 as a novel pharmacological inducer of aberrant vimentin aggregation, presenting a distinct target-driven strategy for antifibrotic drug development.
ER -