Smad7 ameliorate small airway remodeling in COPD by modulating epithelial-mesenchymal transition.

INTRODUCTION: Small airway remodeling is a key pathological feature of COPD, yet its mechanisms remain unclear. TGF-β1 induces epithelial-mesenchymal transition (EMT), contributing to airway remodeling. Smad7 is a negative regulator of TGF-β signaling, but its role in COPD remains undefined. This study investigates whether Smad7 suppresses TGF-β1-induced EMT in COPD small airway remodeling. METHODS: Lung tissues from COPD patients (n=3 for each group) and mouse models (n=5 for each group) were analyzed for EMT markers and collagen deposition. BEAS-2B cells were exposed to cigarette smoke extract (CSE) to assess TGF-β1 secretion. EMT markers (E-Cadherin, N-Cadherin, and Vimentin) were evaluated using RT-qPCR, Western blot, and immunofluorescence staining. Morphological changes were examined, and Smad7 function was assessed via overexpression and knockdown experiments. RESULTS: COPD patients and mouse models showed increased EMT and collagen deposition. CSE exposure upregulated TGF-β1 in BEAS-2B cells, leading to decreased E-Cadherin and increased N-Cadherin and Vimentin. Morphological changes confirmed EMT induction. Overexpression of Smad7 reversed these effects, while its knockdown enhanced them. CONCLUSIONS: Smoking promotes TGF-β1-induced small airway remodeling in COPD by driving EMT. Smad7 suppresses this process.