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 epithelial 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 Ⅰ, 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 Ⅰ collagen expression, alleviated bleomycin-induced 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 conclusion, ICO attenuates EGF-induced EMT in lung epithelial cells and bleomycin-induced pulmonary fibrosis in mice by downregulating EGFR/NF-κB pathway.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |