Identification and validation of the protective gene BCAT2 related to amino acid metabolism in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, with unknown pathogenesis and no effective treatment. Identifying the key molecular of IPF in underlying mechanisms is critical for developing targeted therapies. Differentially expressed genes (DEGs) were identified based on GSE53845 data from the Gene Expression Omnibus (GEO) database and the Limma R package, followed by gene set enrichment analysis (GSEA). The key module genes selected by Weighted Gene Co-expression Network Analysis (WGCNA) were integrated with the DEGs. The hub genes were screened using three machine-learning algorithms, with further performance validated through Receiver Operating Characteristic (ROC) curves and nomogram models. In addition, validation was performed using external validation sets, in vitro experiments and human lung tissues. Enrichment analyses were conducted using GeneMANIA and GSEA. Branched chain amino acid transferase 2 (BCAT2) was identified as a central hub gene in IPF by intersecting key module genes with DEGs through WGCNA and machine learning methods. Experimental validation confirmed the significantly downregulation of BCAT2 in the lung tissues of IPF patients and in TGF-β1-treated alveolar epithelial cells (AECs). Moreover, upregulation of BCAT2 attenuated the expression of fibrosis markers in AECs exposed to TGF-β1. Ultimately, Co-expression analysis and GSEA indicated that BCAT2 is closely involved in several key signaling pathways. Collectively, our findings suggest that BCAT2 is a critical protective molecule in the pathogenesis of IPF and represents a potential therapeutic target for modulating the progression of pulmonary fibrosis.