Accumulation of AIF1 in Lung Fibroblasts Enhances Response to TGF-β and Advances Pulmonary Fibrosis Progression

This study investigates the role of Allograft Inflammatory Factor 1 (AIF1) in lung fibroblasts and its impact on the progression of pulmonary fibrosis, a devastating lung disease characterized by excessive fibrous tissue formation. The research focuses on understanding how the accumulation of AIF1 in lung fibroblasts influences their response to TGF-β1, a key cytokine involved in fibrotic processes. We first identified 15 factors, including AIF1, through transcriptome sequencing and bioinformatics analysis. Subsequently, through further in vitro experiments, we confirmed the important role of AIF1. Through in vitro experiments, we discovered that overexpression of AIF1 can enhance the activity of downstream pathways in fibroblasts under the same concentration of TGF-β1. The downstream pathways is characterized by increased fibroblast activation, proliferation, and differentiation into myofibroblasts – cells that play a central role in fibrosis. Additionally, these AIF1-enriched fibroblasts exhibit elevated production of extracellular matrix components, further contributing to fibrotic tissue deposition。 Conversely, the silencing of AIF1 with siRNA showed the opposite effect. Our findings suggest that AIF1 plays a pivotal role in modulating lung fibroblast reactivity to TGF-β, thereby facilitating the progression of pulmonary fibrosis. This novel insight into the cellular mechanisms of pulmonary fibrosis highlights AIF1 as a potential therapeutic target.