Decoding Dysregulation of DNA Methylation in Epigenetics of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF), the continuously advancing and frequently lethal idiopathic interstitial pneumonia, is pathologically characterized by abnormal deposition of extracellular matrix constituents, leading to progressive pulmonary scarring. Although substantial research efforts have been devoted to elucidating its pathogenesis, the etiology, molecular mechanisms, and effective treatment strategies for IPF remain inadequately characterized, contributing to a median postdiagnostic survival period of merely three to five years. Epigenetic modifications, particularly DNA methylation, have emerged as a potential missing link between the genetic background and environmental risk factors contributing to the pathogenesis of fibrotic disorders, including IPF. DNA methylation entails the attachment of a methyl group to the cytosine residue, frequently occurring at CpG dinucleotides, which are concentrated in clusters known as CpG islands and orchestrates the target gene expression. In this review, we will explore the mechanism of DNA methylation and provide insights into recent advancements concerning its role in major profibrotic cells within lung tissues during the progression of IPF, and by which, we aim to generate valuable evidence that can facilitate the advancement of antifibrotic therapies for clinical applications.