The role of lung type Ⅱ epithelial stem cell differentiation in radiation-induced pulmonary fibrosis
10.3760/cma.j.cn113030-20190811-00323
- VernacularTitle:肺Ⅱ型上皮干细胞分化在放射性肺纤维化中作用
- Author:
Ziting XIAO
1
;
Jian TIAN
;
Yanyan ZHU
;
Chaojie WANG
;
Ning MA
;
Xingnan ZHANG
;
Yun ZHOU
;
Jianwei ZHOU
Author Information
1. 河南大学人民医院肿瘤内科（河南省人民医院肿瘤内科），郑州 450003
- From:
Chinese Journal of Radiation Oncology
2020;29(12):1102-1109
- CountryChina
- Language:Chinese
-
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 β 1(TGF-β 1), 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-β 1 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-β 1 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-β 1, which is a potential cause of radiation-induced pulmonary fibrosis.
