TGF-β1-mediated alterations of rat lung fibroblast differentiation resulting in the radiation-induced fibrotic phenotype
TGF-β1-mediated alterations of rat lung fibroblast differentiation resulting in the radiation-induced fibrotic phenotype
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DOI：
10.1080/095530000138501
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发表时间：
2000-04-01
影响因子：
2.6
通讯作者：
Rodemann, HP
中科院分区：
文献类型：
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作者：
Hakenjos, L;Bamberg, M;Rodemann, HP
目的：研究TGF-β 1和TGF-β中和抗体对辐射后大鼠肺成纤维细胞克隆形成活性和终末分化的影响。应用集落形成测定来确定辐射敏感性以及辐射诱导的分化模式的改变。基于TGF-β 1特异性。ELISA法测定假照射组和照射组培养液中TGF-β 1的含量。对亚融合状态下照射的细胞应用立即（ip）和延迟（dp）接种程序，可以观察到辐射剂量-反应曲线的明显差异（SF 2（ip）0.20 +/- 0.025 vs SF 2（dp）0.51 +/- 0.0077）。在用4戈伊的单剂量照射后，在培养基中发现的TGF-β 1的水平增加了约60%。辐射引起的用PMF：MF比值的变化（0戈伊时为0.8，4戈伊时为3.0）来表示祖细胞成纤维细胞（MF）向有丝分裂后纤维细胞（PMF）的终末分化。针对TGF-β的中和抗体抑制了辐射诱导的大鼠肺成纤维细胞克隆形成活性的降低以及辐射诱导的MF祖细胞成纤维细胞向PMF有丝分裂后fibrocytes.Conclusion的终末分化：结果表明TGF-β 1在触发辐射诱导的大鼠肺成纤维细胞克隆形成活性抑制以及终末分化中的重要作用。提出的数据支持这一假设，终末分化是一个重要的细胞过程中的发展辐射诱导的肺纤维化。
Purpose: To study the influence of TGF-beta 1 and TGF-beta-neutralizing antibodies on the clonogenic activity and terminal differentiation of rat lung fibroblasts following radiation exposure.Material and methods: Early passage rat lung fibroblasts were used in this study. Colony formation assays were applied to determine the radiation sensitivity as well as radiation-induced alterations in differentiation pattern. Based on a TGF-beta 1-specific. ELISA system, the amount of TGF-beta 1 in the culture medium of sham-irradiated and irradiated cultures was determined.Results: Applying immediate (ip) and delayed plating (dp) procedures for cells irradiated in the subconfluent state, distinct differences in the radiation dose-response curves could Le observed (SF2(ip) 0.20 +/- 0.025 versus SF2(dp) 0.51 +/- 0.0077). Upon irradiation with a single dose of 4 Gy the level of TGF-beta 1 found in the culture medium increased by about 60%. Radiation-induced. terminal differentiation of progenitor fibroblasts (MF) to postmitotic fibrocytes (PMF) was expressed by the change of the ratio of PMF:MF (0.8 at 0 Gy versus 3.0 at 4 Gy). Neutralizing antibodies directed against TGF-beta inhibited both the radiation-induced reduction in clonogenic activity of rat lung fibroblasts as well as the radiation-induced terminal differentiation of MF progenitor fibroblasts to PMF postmitotic fibrocytes.Conclusion: The results indicate the important role of TGF-beta 1 in triggering radiation-induced inhibition of clonogenic activity as well as terminal differentiation of rat lung fibroblasts. The data presented support the hypothesis that terminal differentiation is an essential cellular process in the development of radiation-induced fibrosis in the lung.