| 张婷婷,周建炜,岳浩迪,李颜君,耿熙炆,李立,张玉薇,刘小转,田健.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[J].中华放射医学与防护杂志,2022,42(6):422-427 |
| 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 |
| Dynamic phenotype of lung type Ⅱ alveolar epithelial cells in radiation-induced lung injury and its role in the formation of fibrosis |
| 投稿时间：2021-12-23 |
| DOI：10.3760/cma.j.cn112271-20211223-00492 |
| 中文关键词: 放射性肺损伤 肺Ⅱ型上皮细胞 细胞表型 上皮间质转化 肺纤维化 |
| 英文关键词:Radiation-induced lung injury Type Ⅱalveolar epithelial cells Cell phenotype Epithelial-mesenchymal transition Fibrogenesis |
| 基金项目:国家自然科学基金(81673097) |
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| 中文摘要: |
| 目的 探究在放射性肺损伤小鼠模型中肺Ⅱ型上皮细胞(AEC Ⅱ)细胞表型动态变化及其在放射性肺纤维化形成中的机制。方法 90只C57BL/6J雌性小鼠按随机数表法分为照射组和假照射组：照射组(50只，X射线单次胸部照射20 Gy)，假照射组(40只，假照射)。分别于照射24 h、4周、12周后处死5只小鼠取肺组织用于肺组织病理学观察；同期另取肺组织用磁珠分选法分离原代AECⅡ，采用RT-PCR法检测proSP-C、HOPX、vimentin、β-catenin和TGF-β1 mRNA表达水平。结果 照射组小鼠肺组织病理学结果显示射线照射24 h后表现为急性放射性肺炎，在照射4周后炎症减轻，同时伴有部分肺泡间隔增厚和少量胶原沉积。照射12周后，胶原沉积显著，肺泡腔塌陷融合，肺泡间隔异常增生，肺纤维化形成；原代AECⅡ内proSP-C和HOPX的mRNA相对表达量均在照射24 h后开始升高，并同时在照射4周后达到峰值(F=8.441、3.586，P=0.036)；vimentin的mRNA相对表达量也在照射4周后明显增加，并持续至照射12周后(F=8.358，P=0.001)；β-catenin和TGF-β1的mRNA相对表达量在射线照射后均升高，并在照射12周后显著高表达(F=4.623、279，P=0.044)。结论 AEC Ⅱ不仅通过细胞表型从proSP-C+→HOPX+/proSP-C+→HOPX+/proSP-C+/vimentin+ →vimentin+/proSP-C的转换，同时通过异分化为间质细胞，高表达促纤维因子，诱导EMT的发生，参与放射性肺损伤的修复和放射性纤维化的形成。 |
| 英文摘要: |
| 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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