m 6 A methylation regulatory network in pulmonary fibrosis: Molecular mechanisms from RNA stability to cellular phenotype transition (Review)

Pulmonary fibrosis (PF) is a progressive and often irreversible interstitial lung disease characterized by aberrant wound healing, excessive extracellular matrix deposition and distortion of lung architecture.N6-methyladenosine (m 6 A), the most abundant internal modification in eukaryotic mRNA, dynamically regulates RNA metabolism through m 6 A writers, erasers and readers.Evidence indicates that m 6 A dysregulation contributes to PF by modulating fibroblast activation, epithelial injury and senescence, epithelial-mesenchymal plasticity, macrophage-associated inflammation, oxidative stress responses and extracellular matrix remodeling.In the present review, the expression characteristics and functional alterations of m 6 A machinery in fibrotic lung tissue, the role of m 6 A-mediated epitranscriptomic remodeling in pulmonary cell fate determination and the potential translational value of m 6 A regulators as biomarkers and therapeutic targets are summarized.In addition, particular focus is placed on cell-type-specific and context-dependent mechanisms, including the distinct roles of METTL3, METTL14, FTO, ALKBH5 and YTHDF proteins in different fibrotic settings.The present review highlights that m 6 A modification is not a uniform pro-fibrotic or anti-fibrotic switch, but rather a dynamic regulatory network that links RNA metabolism to PF progression and therapeutic opportunities.