RNA Modifications as Molecular Regulators of Alveolar Epithelial Injury and Aberrant Repair in Pulmonary Fibrosis

Pulmonary fibrosis is a progressive interstitial lung disease characterized by persistent alveolar epithelial injury, aberrant repair, and excessive extracellular matrix deposition. Increasing evidence indicates that disease progression is closely associated with alveolar type II (AT2) cell dysfunction, impaired AT2-to-AT1 differentiation, and the persistence of transitional epithelial populations, including KRT8+ intermediate populations. Because the formation and resolution of these transitional epithelial populations require dynamic regulation of stress-responsive transcripts and differentiation-associated RNA programs, they provide a biologically relevant context for investigating RNA modification-mediated post-transcriptional regulation. RNA modifications have emerged as post-transcriptional regulatory layers that modulate RNA stability, processing, translation efficiency, and stress-response gene expression, thereby influencing epithelial stress adaptation and repair-related state transitions. Among these modifications, N6-methyladenosine (m6A) is the best-characterized layer, with evidence linking it to epithelial injury responses, senescence-associated transcript remodeling, and differentiation impairment. In contrast, non-m6A modifications, including m5C, m1A, m7G, pseudouridine (Ψ), and A-to-I RNA editing, remain emerging regulatory layers with limited AT2 cell-specific functional validation. This review summarizes current evidence connecting RNA modifications with alveolar epithelial injury, transitional-state persistence, epithelial–mesenchymal communication, and fibrotic remodeling. Rather than interpreting RNA modifications as isolated pathogenic drivers, we highlight their context-dependent roles in RNA fate control, epithelial stress adaptation, and aberrant repair in pulmonary fibrosis.