Reduced irradiation pulmonary fibrosis and stromal cell migration in Smad3-/- marrow chimeric mice.
Reduced irradiation pulmonary fibrosis and stromal cell migration in Smad3-/- marrow chimeric mice.
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发表时间：
2006-09
期刊：
影响因子：
2.3
通讯作者：
M. Epperly;D. Franicola;Xi-chen Zhang;S. Nie;Hong Wang;A. Bahnson;D. Shields;J. Goff;Hongmei Shen;J. Greenberger
中科院分区：
文献类型：
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作者：
M. Epperly;D. Franicola;Xi-chen Zhang;S. Nie;Hong Wang;A. Bahnson;D. Shields;J. Goff;Hongmei Shen;J. Greenberger
肺辐照纤维化涉及骨髓来源的肌成纤维细胞祖细胞（骨髓基质细胞）向肺的迁移。Smad3-/-小鼠表现出电离照射诱导的皮肤纤维化减少、骨软骨形成缺陷和其他被认为与基质细胞对转化生长因子β (tgffβ)反应缺陷相关的异常。克隆骨髓间质细胞系来源于纯合子缺失重组阴性Smad3-/-小鼠和Smad3+/+仔鼠连续骨髓培养的贴壁层。在自动细胞跟踪系统中对5天内体外单细胞迁移能力的定量分析表明，与Smad3+/+克隆MSC系相比，Smad3-/-每24小时的移动微米数显著减少。通过逆转录病毒载体转染Smad3而非对照ds-red转基因重新表达，恢复了体外迁移能力。在20 Gy照射C57BL/6J小鼠肺后80天内，静脉注射GFP转基因产品标记的Smad3-/- (MSCs)的增殖效率比ds-red转基因产品标记的Smad3+/+细胞低10倍，并且在细胞注射后60天内增殖不明显。与Smad3+/+骨髓嵌合的雌性小鼠相比，Smad3-/-嵌合的雌性小鼠显示辐照后肺纤维化减少，Y+基质细胞向肺部迁移，生存率提高。数据显示，Smad3-/-骨髓基质细胞体内和体外迁移能力的降低与Smad3-/-骨髓嵌合小鼠放射性肺纤维化的减少有关。
Pulmonary irradiation fibrosis involves migration to the lungs of bone marrow origin myofibroblast progenitor cells (marrow stromal cells (MSCs)). Smad3-/- mice display decreased ionizing irradiation-induced skin fibrosis, defective osteochondrogenesis and other abnormalities thought to be associated with a defective stromal cell response(s) to transforming growth factor-beta (TGFFbeta). Clonal bone marrow stromal cell lines were derived from the adherent layer of continuous bone marrow cultures of homozygous deletion recombinant negative Smad3-/- mice and Smad3+/+ littermates. Quantitation in an Automated Cell Tracking System of the in vitro single cell migratory capacity over five days demonstrated a significant decrease in locomotion in microns per 24 h of Smad3-/- compared to Smad3+/+ clonal MSC lines. Reexpression by retroviral vector transfection of the Smad3 but not control ds-red transgene restored in vitro migratory capacity. Intravenously injected GFP transgene product labeled Smad3-/- (MSCs) seeded 10-fold less effectively than ds-red transgene product labeled Smad3+/+ cells to the 80 days post 20 Gy irradiated lungs of C57BL/6J mice and proliferated less significantly for 60 days after cell injection. Female mice chimeric for male Smad3-/- compared to Smad3+/+ marrow showed decreased irradiation pulmonary fibrosis, Y+ stromal cell migration to the lungs, and improved survival. The data show that the reduced in vitro and in vivo migratory capacity of Smad3-/- bone marrow stromal cells correlates with decreased radiation pulmonary fibrosis observed in mice chimeric for Smad3-/- marrow.