Background: Radiation therapy is commonly used to treat thoracic malignancies. However, it may lead to severe lung pneumonitis and ultimately fibrosis. Irradiation has been reported to increase epithelial-mesenchymal transition (EMT) of type II alveolar epithelial cells (AEC), which play an important role in pulmonary fibrosis. The transforming growth factor-β (TGF-β) and ERK/glycogen synthase kinase 3β (GSK3β) pathways are critically involved in radiation-induced EMT. In the present study, we investigated whether baicalin was a novel therapeutic candidate for radiation-induced EMT in type II AEC.
Methods: Primary type II AEC were isolated and treated with 60Co γ-rays and a series doses of baicalin (2μM, 10μM and 50μM). The ultrastructure and morphology changes were observed by transmission electron microscopy and optical microscopy, respectively. Protein expression was determined by western blotting analysis. Immunofluorescence staining was performed to detect the nuclear translocation of Snail.
Results: After irradiation, type II AEC displayed a mesenchymal-like morphology accompanied by a decrease in E-cadherin expression, an increase in the expression of Vimentin and α-SMA. Nuclear translocation of Snail, the activation of TGF-β/Smad pathway, and the inactivation of GSK3β were prominent in radiation-treated cells. Baicalin significantly attenuated the effects of radiation on type II AEC.
Conclusions: Baicalin may a useful radioprotective agent through suppressing the EMT of type II AEC.
Keywords: Baicalin; EMT; ERK/GSK3β; Radiation; TGF-β.
Copyright © 2017. Published by Elsevier Masson SAS.