Dynamic phenotype of lung type Ⅱ alveolar epithelial cells in radiation-induced lung injury and its role in the formation of fibrosis
10.3760/cma.j.cn112271-20211223-00492
- VernacularTitle:放射性肺损伤中肺Ⅱ型上皮细胞的动态表型及其在纤维化形成中的作用机制研究
- Author:
Tingting ZHANG
1
;
Jianwei ZHOU
;
Haodi YUE
;
Yanjun LI
;
Xiwen GENG
;
Li LI
;
Yuwei ZHANG
;
Xiaozhuan LIU
;
Jian TIAN
Author Information
1. 郑州大学人民医院河南省人民医院临床单细胞生物医学中心，郑州 450000
- Keywords:
Radiation-induced lung injury;
Type Ⅱalveolar epithelial cells;
Cell phenotype;
Epithelial-mesenchymal transition;
Fibrogenesis
- From:
Chinese Journal of Radiological Medicine and Protection
2022;42(6):422-427
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the dynamic phenotype of type Ⅱ alveolar epithelial cells(AEC Ⅱ)in radiation-induced lung fibrosisand its role in the formation of fibrosis.Methods:Totally 90 C57BL/6J female mice were divided into 2 groups: irradiation group (50, thoracic irradiation with a single dose of 20 Gy X-rays), control group (40, sham irradiation). At 24 h, 4 and 12 weeks after irradiation, 5 mice were euthanized and the lungs were collected for pathological observation. The other lungtissues were collected for the isolation of primary AEC Ⅱ cells with microbeadssorting.The mRNA expressions of proSP-C, HOPX, vimentin, β-catenin and TGF-β1 in AEC II cells were detected by RT-PCR.Results:Acute pneumonitis was observed in the lungs at 24 h after irradiation and alleviated in accompany with partial alveolar septal thickening and a small amount of collagen deposition at 4 weeks after irradiation. The collagen deposition became more pronounced at 12 weeks after irradiation, together with collapsed and fused alveolar cavities, alveolar septal hyperplasia, and pulmonary fibrosis formation.The mRNAexpression levels of proSP-C and HOPX in primary AEC Ⅱ cells increased at 24 hours after irradiation and then approached to a peak value at 4 weeks after irradiation ( F=8.441, 3.586, P=0.036). The mRNA expression levels of vimentin, a biomarker of EMT, was increased significantly at 4 weeks and continued up to 12 weeks after irradiation( F=8.358, P=0.001). The mRNA expression levels of profibrotic factors β-catenin and TGF-β1 were both significant increased at 12 weeks after irradiation( F=4.62, 3.279, P=0.044). Conclusions:The phenotypeof AECⅡ cells could not only be transformed from proSP-C+ to HOPX+ /proSP-C+ , HOPX+ /proSP-C+ /vimentin+ , and vimentin+ /proSP-C, but also differentiated into mesenchymal cells with highly expressed profibrotic factors, thereby inducing EMT process, which either played a role in the repair of radiation-induced lung injury or triggered radiation-induced fibrosis.
