Identification of potential biomarkers for idiopathic pulmonary fibrosis and validation of TDO2 as a potential therapeutic target

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a high mortality rate. On this basis, exploring potential therapeutic targets to meet the unmet needs of IPF patients is important. AIM To explore novel hub genes for IPF therapy. METHODS Here, we used public datasets to identify differentially expressed genes between IPF patients and healthy donors. Potential targets were considered based on multiple bioinformatics analyses, especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide, forced vital capacity, and patient survival rate. The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction. RESULTS We found that TDO2 was upregulated in IPF patients and predicted poor prognosis. Surprisingly, single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts, indicating that TDO2 may participate in the regulation of proliferation and survival. Therefore, we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-beta (TGF-beta)-induced pulmonary fibrosis. Furthermore, the results showed that a TDO2 inhibitor effectively suppressed TGF-beta-induced fibroblast activation. These findings suggest that TDO2 may be a potential target for IPF treatment. Based on transcription factors-microRNA prediction and scRNA-seq analysis, elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis. CONCLUSION We provided new target genes prediction and proposed blocking TGF-beta production as a potential treatment for IPF.