Icotinib Improves Bleomycin-Induced Pulmonary Fibrosis by Inhibiting Epithelial-Mesenchymal Transition of Alveolar Epithelial Cells
OBJECTIVE This study aimed to investigate the role and potential mechanisms of Icotinib(ICO)on pulmonary fibrosis.METHODS C57BL/6 mice were randomly divided into Sham group,PF group,ICO 30 mg·kg-1 group and ICO 60 mg·kg-1 group,8 rats in each group.A mouse model of PF was induced by intratracheal injection of bleomycin(3 mg·kg-1).Hematoxylin-eosin staining and Masson trichrome staining for lung tissues were performed to observe the pathological alterations and collagen deposition.Immunohistochemical detection of lung tissue collagen type Ⅰ(collagen Ⅰ)expression.In vitro,the lung epithe-lial cells were divided into control group,epidermal growth factor(EGF)group,EGF combined with ICO(0.1,1,10 mmol·L-1)groups.The protein expression of E-cadherin,α-SMA and nuclear transfer of NF-κB p65 were detected by immunofluorescence.The protein levels of Collagen 1,E-cadherin,α-SMA,Vimentin,phosphorylation epidermal growth factor receptor(p-EGFR),p-IκBα,p-NF-κB p65 and nuclear NF-κB p65 were detected by Western blot analysis in lung tissue and(or)cells.RESULTS The results demonstrated that ICO inhibited bleomycin-induced collagen deposition,reduced type 1 collagen expression,alleviated bleomycin-in-duced EMT(increased E-cadherin expression and decreased Vimentin and α-SMA expression),and decreased phosphorylation of EGFR,IκBα,NF-κB p65 and nuclear translocation of NF-κB p65 in vivo.Furthermore,incubation of lung epithelial cells with EGF activated EMT and EGFR/NF-κB signaling pathway,and these effects were reversed by ICO In vitro.CONCLUSION In conclu-sion,ICO attenuates EGF-induced EMT in lung epithelial cells and bleomycin-induced pulmonary fibrosis in mice by downregulating EGFR/NF-κB pathway.
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