Association of interferon regulator factor 1 upregulation with pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a complex disease that is associated with a poor prognosis. Its pathogenesis is attributed to the inflammatory immune response. Interferon regulator factor 1 (IRF1) is a key downstream regulator of inflammation and cell death. Evidence suggests that IRF1 can promote the proliferation of smooth muscle cells and inhibit lung endothelial regeneration. However, proof for this relationship is lacking, and the exact nature of the potential mechanism underlying the link between IRF1 and PAH remains largely unknown. We aimed to find out whether IRF1 is associated with the progression of PAH. Methods: The GSE144274 and GSE243193 datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PAH and healthy samples were identified and analyzed. Enrichment analysis was performed, and a protein-protein interaction (PPI) network was constructed to identify the hub genes. The relative protein and gene levels of IRF1 were then validated in PAH animal models. Results: A total of 271 DEGs were identified from the two data sets. ACTA2, HLA-DRA, HLA-A, PECAM1, HLA-C, IRF1, and CD74 were identified as the hub genes. In our subsequent experiments, we found that IRF1 was upregulated in both PAH rat and mouse models. Conclusions: Our findings suggest that IRF1 might be associated with pulmonary hypertension in lung tissue and may thus serve as a therapeutic target in PAH.