Resveratrol Improves Idiopathic Pulmonary Fibrosis by Targeting IKZF3.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited treatment options. This study investigates the therapeutic potential of resveratrol, a natural compound, in treating IPF by targeting IKZF3, a transcription factor upregulated in IPF patients. Using bioinformatics analysis of the GSE110147 dataset, we identified IKZF3 as a key molecule in IPF progression. In vitro experiments with bleomycin (BLM)-treated A549 cells showed that IKZF3 overexpression exacerbated cell death and fibrosis, while its silencing reversed these effects. Resveratrol treatment significantly improved cell viability, reduced fibrosis markers, and inhibited IKZF3's transcriptional regulation of IL-33, which in turn decreased ILC-2 activation. Molecular docking revealed a strong binding affinity between resveratrol and IKZF3. In vivo validation using a BLM-induced IPF mouse model demonstrated that resveratrol reduced lung fibrosis and downregulated fibrosis-related markers. Our findings suggest that targeting IKZF3 with resveratrol may offer a novel therapeutic strategy for IPF, highlighting the potential of this combination to improve disease outcomes.