Transcriptomic analysis of Platycodin D (PD)-improved idiopathic pulmonary fibrosis (IPF) mice

This study focuses on the role of PD, a natural compound derived from traditional Chinese medicine, in the prevention and treatment of IPF, a disease in which pulmonary fibroblast-to-myofibroblast transdifferentiation is a key pathogenic driver. By employing both in vivo and in vitro IPF models, combined with techniques including transcriptome analysis, Lip-SMap, molecular docking, molecular dynamics simulations, Cellular Thermal Shift Assay (CETSA), and Surface Plasmon Resonance (SPR), the research demonstrates that PD alleviates lung injury, mitigates systemic and pulmonary inflammation, reduces oxidative stress, and notably suppresses myofibroblast transdifferentiation in IPF models. Further mechanistic investigations identify PPP2R1A as a direct target of PD; PD stabilizes and activates protein phosphatase 2A (PP2A) by binding to PPP2R1A, thereby inhibiting the PI3K/Akt signaling pathway. Collectively, these findings indicate that PD exerts anti-IPF effects at least partially through the PPP2R1A/PP2A/PI3K/Akt axis, highlighting its potential value as a therapeutic agent targeting myofibroblast transdifferentiation in IPF management. Overall design: IPF models were used to assess the effects of PD on inflammation, oxidative stress, and fibroblast-to-myofibroblast transdifferentiation. Core targets and mechanisms were identified using a comprehensive assay, which comprised transcriptome analysis and the Lip-SMap technology. Molecular docking, molecular dynamics simulations, CETSA, SPR, and functional recovery experiments were performed to validate the direct targets of PD and elucidate its anti-IPF molecular actions.