| Zhang Tingting,Zhou Jianwei,Yue Haodi,et al.Dynamic phenotype of lung type Ⅱ alveolar epithelial cells in radiation-induced lung injury and its role in the formation of fibrosis[J].Chinese Journal of Radiological Medicine and Protection,2022,42(6):422-427 |
| Dynamic phenotype of lung type Ⅱ alveolar epithelial cells in radiation-induced lung injury and its role in the formation of fibrosis |
| Received:December 23, 2021 |
| DOI：10.3760/cma.j.cn112271-20211223-00492 |
| KeyWords:Radiation-induced lung injury Type Ⅱalveolar epithelial cells Cell phenotype Epithelial-mesenchymal transition Fibrogenesis |
| FundProject:国家自然科学基金(81673097) |
| Author Name | Affiliation | E-mail | | Zhang Tingting | Center for Clinical Single-Cell Biomedicine, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Zhou Jianwei | Department of Oncology, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Yue Haodi | Center for Clinical Single-Cell Biomedicine, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Li Yanjun | Center for Clinical Single-Cell Biomedicine, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Geng Xiwen | Center for Clinical Single-Cell Biomedicine, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Li Li | Center for Clinical Single-Cell Biomedicine, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Zhang Yuwei | Center for Clinical Single-Cell Biomedicine, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Liu Xiaozhuan | Center for Clinical Single-Cell Biomedicine, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | | | Tian Jian | Department of Oncology, Henan Provincial People′s Hospital, People′s Hospital of Zhengzhou University, School of Clinical Medicine, Zhengzhou 450000, China | jacktian12@gmail.com |
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| 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. |
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