Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity.
Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity.
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DOI：
10.1186/1471-2407-5-59
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发表时间：
2005-06-10
期刊：
影响因子：
3.8
通讯作者：
Vujaskovic, Z
中科院分区：
文献类型：
--
作者：
Rabbani, ZN;Anscher, MS;Folz, RJ;Archer, E;Huang, H;Chen, LG;Golson, ML;Samulski, TS;Dewhirst, MW;Vujaskovic, Z
急性rt诱导的肺损伤以炎症变化为特征，炎症变化在损伤后期发展为纤维化病变。最终，如果炎症/纤维化介质和氧化应激的来源没有被清除或减弱，将会发生完全的结构性消融。因此，本研究的目的是确定小鼠细胞外超氧化物歧化酶（EC-SOD）的过表达是否通过抑制tgf - β1的激活和下调其信号转导途径的Smad 3臂来改善急性辐射损伤。对过表达EC-SOD的转基因（XRT-TG）和野生型（XRT-WT）动物进行全胸单剂量辐射（15 Gy）。小鼠分别于第1天、第1周、第3周、第6周、第10周和第14周处死。评估呼吸频率、右肺重量、总/差异白细胞计数、活化tgf - β1及其信号转导通路组分（Smad 3和p-Smad 2/3）以确定肺损伤。辐照野生型（XRT-WT）小鼠呼吸频率和右肺重量随时间的增加而增加，而转基因（XRT-TG）小鼠在第3、6、10和14周时这些参数的增加明显较少（p < 0.05）。在XRT-WT小鼠中发现以巨噬细胞浸润为主要特征的炎症反应。在1、3、6和14周时，XRT-TG小鼠的急性炎症明显减轻（p < 0.05）。与XRT-WT相比，XRT-TG较晚时间点活化tgf - β1及其信号转导通路组分的表达显著降低（p < 0.05）。本研究表明，过表达EC-SOD对rt诱导的急性肺损伤具有保护作用。EC-SOD似乎在一定程度上通过抑制巨噬细胞反应起作用，也通过随后下调促纤维化tgf - β通路降低tgf - β1的激活。
Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed to the development of fibrotic lesions in the late phase of injury. Ultimately, complete structural ablation will ensue, if the source of inflammatory / fibrogenic mediators and oxidative stress is not removed or attenuated. Therefore, the purpose of this study is to determine whether overexpression of extracellular superoxide dismutase (EC-SOD) in mice ameliorates acute radiation induced injury by inhibiting activation of TGFβ1 and downregulating the Smad 3 arm of its signal transduction pathway. Whole thorax radiation (single dose, 15 Gy) was delivered to EC-SOD overexpressing transgenic (XRT-TG) and wild-type (XRT-WT) animals. Mice were sacrificed at 1 day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung weights, total/differential leukocyte count, activated TGFβ1 and components of its signal transduction pathway (Smad 3 and p-Smad 2/3) were assessed to determine lung injury. Irradiated wild-type (XRT-WT) animals exhibited time dependent increase in breathing rates and right lung weights, whereas these parameters were significantly less increased (p < 0.05) at 3, 6, 10 and 14 weeks in irradiated transgenic (XRT-TG) mice. An inflammatory response characterized predominantly by macrophage infiltration was pronounced in XRT-WT mice. This acute inflammation was significantly attenuated (p < 0.05) in XRT-TG animals at 1, 3, 6 and 14 weeks. Expression of activated TGFβ1 and components of its signal transduction pathway were significantly reduced (p < 0.05) at later time-points in XRT-TG vs. XRT-WT. This study shows that overexpression of EC-SOD confers protection against RT-induced acute lung injury. EC-SOD appears to work, in part, via an attenuation of the macrophage response and also decreases TGFβ1 activation with a subsequent downregulation of the profibrotic TGFβ pathway.
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DOI：
10.1152/ajplung.00058.2001
发表时间：
2002-04-01
影响因子：
4.9
作者：
Bowler, RP;Nicks, M;Crapo, JD
通讯作者：
Crapo, JD
DOI：
10.1016/0360-3016(90)90541-q
发表时间：
1990-08-01
影响因子：
7
作者：
GRAHAM, MM;EVANS, ML;RASEY, JS
通讯作者：
RASEY, JS
DOI：
10.1164/ajrccm.162.1.9903129
发表时间：
2000-07-01
影响因子：
24.7
作者：
Hagiwara, S;Ishii, Y;Kitamura, S
通讯作者：
Kitamura, S
影响因子：
56.9
作者：
ODA, T;AKAIKE, T;MAEDA, H
通讯作者：
MAEDA, H
影响因子：
3.4
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
通讯作者：
Finkelstein, JN