Jinshui Liujun Decoction attenuates cigarette smoke-induced small airway remodeling via the TGF-β/Smad2/CFTR Axis

Small airway remodeling is a key pathological feature of chronic obstructive pulmonary disease (COPD), and epithelialmesenchymal transition (EMT) is among the central mechanisms driving this remodeling process. Jinshui Liujun Decoction (JSLJD), a traditional Chinese herbal formula, has shown therapeutic potential in respiratory diseases, but its effects on COPD-associated small airway remodeling remain unclear. In this study, JSLJD significantly reduced collagen accumulation, airway wall thickening, and α-SMA expression in the lungs of cigarette smoke (CS)-exposed mice. In vivo and in vitro, JSLJD inhibited EMT, as reflected by elevated E-cadherin expression and reduced vimentin, fibronectin, and Snail expression. Mechanistically, JSLJD inhibited TGF-β/Smad2 activation and restored cystic fibrosis transmembrane conductance regulator (CFTR) expression. Pharmacological blockade of CFTR or activation of TGF-β abrogated the anti-EMT effects of JSLJD. In conclusion, JSLJD alleviates CS-induced small airway remodeling by suppressing EMT via the inhibition of the TGF-β/Smad2 pathway and the recovery of CFTR function, highlighting its promise as a prospective therapy for COPD.