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2 Key regulatory mechanisms of EMT 2.1 Central role of TGF- superfamily signaling As a pleiotropic cytokine, transforming growth factor- (TGF-) exerts pivotal regulatory functions in pulmonary fibrosis via both Smad-dependent and Smad-independent pathways, driving epithelialmesenchymal transition (EMT) and promoting airway inflammation and remodeling ( The TGF-/Smad cascade also contributes to airway fibrosis through induction of amphiregulin (AREG), which activates EGFR signaling to enhance fibroblast proliferation and myofibroblast conversion