Abstract：Objective To determine the role of type Ⅱ alveolar epithelial stem cells (AEC Ⅱ) in radiation-induced pulmonary injury and investigate the potential mechanism by observing the dynamic changes in the expression levels of anti-prosurfactant protein C (proSP-C) proSP-C (AEC Ⅱ biomarker), homeobox only protein X (HOPX, type I alveolar epithelial cell biomarker) or vimentin (a mesenchymal marker) and transforming growth factor β1(TGF-β1), a profibrotic cytokine. Methods Eight-week old C57BL/6j female mice were exposed to X-ray thoracic irradiation. Mouse lungs were collected at 8 different time points of 24 h, 1 week, 1 to 6 months after irradiation. The histopathological changes of the lungs at different time points were observed with H& E staining to determine the time of formation of pulmonary fibrosis. In addition, the co-expression of proSP-C with HOPX or vimentin in AEC Ⅱ was confirmed by immunofluorescence staining to track AEC Ⅱ phenotypes at different injury phases following thoracic irradiation. The expression levels of those proteins and TGF-β1 were quantitatively detected by Western blot. Results After thoracic exposure to a single dose of 20 Gy X-ray for 3 months, the fibrotic lesions in the lungs could be noted. The co-expression of proSP-C with vimentin or HOPX could be observed in AEC Ⅱ. Western blot demonstrated that the expression levels of TGF-β1 and those proteins were also changed along with the lung injury. Conclusion AEC Ⅱ can be differentiated into mesenchymal-like cells after X-ray irradiation due to the up-regulated expression of TGF-β1, which is a potential cause of radiation-induced pulmonary fibrosis.
Xiao Ziting,Tian Jian,Zhu Yanyan et al. The role of lung type Ⅱ epithelial stem cell differentiation in radiation-induced pulmonary fibrosis[J]. Chinese Journal of Radiation Oncology, 2020, 29(12): 1102-1109.
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