Pulmonary fibrosis and exosomes: pathways to treatment

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease characterized by excessive extracellular matrix (ECM) deposition, fibroblast proliferation, and epithelial injury. Disease progression involves key signaling pathways-TGF-β, WNT/β-catenin, PI3K/AKT, and YAP/TAZ-that drive fibroblast activation, epithelial-to-mesenchymal transition (EMT), endothelial-mesenchymal transition (EndMT), and ECM remodeling. Recent studies have highlighted the role of small extracellular vesicles (sEVs), particularly exosomes, as crucial modulators of the fibrotic microenvironment. These vesicles carry microRNAs (miRNAs), proteins, and lipids that influence fibroblast behaviour, immune signaling, and tissue architecture.Growing evidence supports the therapeutic promise of exosomes and engineered nanoparticle-exosome hybrids in targeting dysregulated fibrotic pathways and promoting tissue repair. This review examines the molecular mechanisms underlying pulmonary fibrosis, focusing on the role of exosomal crosstalk and therapeutic potential. We also incorporate emerging insights from single-cell RNA sequencing (scRNA-seq) on fibroblast heterogeneity, the influence of senescence-associated secretory phenotype (SASP) on exosomal cargo, and the limitations of current animal models in recapitulating chronic IPF. Understanding these mechanisms may facilitate the development of precision medicine approaches for managing and potentially reversing IPF progression.