Epigenetic regulatory mechanisms and translational applications in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, relentlessly progressive interstitial lung disease with limited treatment options and poor survival. Existing antifibrotic agents slow functional decline but do not halt or reverse established fibrosis, highlighting the need for IPF specific mechanistic understanding and new therapeutic targets. This review summarizes epigenetic regulatory mechanisms that are implicated in IPF, including DNA methylation, histone modifications, non-coding RNAs, and RNA modifications. These mechanisms can be viewed as interacting networks that reprogramme gene expression in alveolar epithelial cells, macrophages and fibroblasts, leading to impaired epithelial repair, profibrotic immune activation and maintenance of a chronically activated myofibroblast state. The contribution of cell type specific epigenetic signatures to chronic inflammation, disordered tissue remodelling and progressive extracellular matrix accumulation in IPF is underscored. Recent work that translates epigenetic insights into applications for IPF is also reviewed, with a focus on epigenetic marks and regulators as biomarkers for diagnosis, prognosis and treatment response, and as targets for small molecule drugs, nucleic acid based therapies and epigenome editing strategies. Overall the evidence assembled here provides a framework that focuses on IPF epigenetic regulation and can inform experimental design and support the development of more precise therapeutic approaches for patients with IPF.