2. Academic Validation
  3. Cinobufotalin Ameliorates the Development of Pulmonary Fibrosis by Suppressing the TGF-β/Smad Pathway via Regulating PI15

Cinobufotalin Ameliorates the Development of Pulmonary Fibrosis by Suppressing the TGF-β/Smad Pathway via Regulating PI15

  • J Cell Mol Med. 2025 Aug;29(16):e70788. doi: 10.1111/jcmm.70788.
Dong Xia 1,  Xingyan Liu 1,  Qiuting Yang 1,  Jie Li 1,  Li Li 1,  Yong You 2,  Jing Wang 2,  Weiyi Fang 3,  Huiling Yang 1
Affiliations

Affiliations

  • 1 The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, China.
  • 2 Department of Respiratory Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, China.
  • 3 Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
PMID: 40845143 DOI: 10.1111/jcmm.70788
Abstract

Pulmonary fibrosis (PF) is a common hallmark of several types of interstitial lung diseases (ILDs), for which effective therapeutic drugs are lacking. The small-molecule chemical compound cinobufotalin (CB) has demonstrated significant anti-cancer effects in lung Cancer. In this study, we first found that CB attenuated bleomycin (BLM)-induced PF and inhibited transforming growth factor-beta 1 (TGF-β1)-induced myofibroblast activation and epithelial-mesenchymal transition (EMT). Subsequently, comparative RNA Sequencing (RNA-Seq) was conducted to analyse the lung gene expression profiles in mice. Interestingly, peptidase inhibitor 15 (PI15) was identified as a significantly differentially expressed gene (DEG) and may be a potential target in PF progression. Mechanistic studies showed that CB exerts anti-PF effects by inhibiting PI15 and thereby regulating the TGF-β/Smad signalling pathway. Our data demonstrated that CB represents a promising anti-PF drug and may be a candidate therapeutic for PF patients.

Keywords

EMT; PI15; TGF‐β/Smad pathway; cinobufotalin; pulmonary fibrosis.

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