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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.
Pubmed ID: 40845143
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Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
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