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

Small airway remodeling is widely recognized as one of the major pathological changes 11 in chronic obstructive pulmonary disease (COPD), yet the underlying mechanisms remain 12 unclear. In the present study, we observed higher levels of epithelial-mesenchymal transition 13 (EMT) and increased collagen deposition in the lungs of both COPD patients and mice 14 models compared to the control group. Additionally, exposure to cigarette smoke extract 15 (CSE) led to an upregulation of TGF-β1 secretion in bronchial epithelial cells BEAS-2B. Further 16 analyses revealed that TGF-β1 upregulated E-Cadherin and downregulated N-cadherin and 17 Vimentin, as confirmed by rt-qPCR, Western Blot, and Immunofluorescence staining. 18 Morphological changes were also observed as a result of TGF-β1 induction. Interestingly, 19 these TGF-β1-induced changes could be reversed by overexpression of Smad7, while they 20 were enhanced by gene interference. In conclusion, smoking may contribute to TGF-β1–21 induced small airway remodeling, which can be reversed by modulating the EMT process 22 through Smad7.