Effects of Antifibrotic Drugs on Transcriptome of Peripheral Blood Mononuclear Cells in Idiopathic Pulmonary Fibrosis [IPF_PBMC]

Two antifibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells are immunocompetent cells that can predispose to those within the lungs and orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in bulk peripheral blood mononuclear cells of patients with IPF and the effects of antifibrotic drugs on these signatures. Differentially expressed genes (DEGs) were analyzed in patients with IPF and healthy controls, before and after antifibrotic treatment. Enrichment analysis suggested that fatty acid elongation interferes with profibrotic TGF-β/ signaling and production of oxidative stress since treatment with NTD upregulated the elongation enzymes ELOVL6 and ELOVL7. Treatment with PFD downregulated COL1A1 which produces wound-healing collagens, as activated monocyte-derived macrophages during tissue damage participate in the production of collagen, type I, and alpha 1. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinases activation, and inhibition of PAI-1 activity attenuates lung fibrosis. DEGs analysis suggested that both PFD and NTD upregulated SERPINE1 which in turn regulates PAI-1 activity. This study detected different DEGs as a result of PFD and NTD treatments, suggesting different mechanistic roles for the two antifibrotic drugs.