Laminin 332 Deposition is Diminished in Irradiated Skin in an Animal Model of Combined Radiation and Wound Skin Injury
Laminin 332 Deposition is Diminished in Irradiated Skin in an Animal Model of Combined Radiation and Wound Skin Injury
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DOI：
10.1667/rr2422.1
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发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Lazarova, Z.
中科院分区：
文献类型：
--
作者：
Jourdan, M. M.;Lopez, A.;Lazarova, Z.
M.D. M.，洛佩斯，A.，Olasz，E. B.，邓肯，N. E、Demara，M.，Kittipongdaja，W.，鱼，B。L.，马德尔，M.，Schock，A.，Morrow，N.五、塞门年科，弗吉尼亚州，贝克，J.E.，Moulder，J. E. Lazarova，Z.层粘连蛋白332沉积在辐射和创伤性皮肤损伤联合动物模型中的辐射皮肤中减少。Radiat. 176，636-648（2011）.皮肤暴露于电离辐射会影响正常的伤口愈合过程，并极大地影响受影响个体的预后。我们研究了电离辐射对复合辐射和创伤皮肤损伤的大鼠模型中的创伤愈合的影响。使用软X射线束，将单剂量电离辐射（10-40戈伊）输送至皮肤，而不会显著暴露于内脏。照射后1小时，在每只大鼠背部制作两个皮肤伤口。对照组和实验组动物在照射后3、7、14、21和30天处死。测量伤口面积，并评估组织样本的层粘连蛋白332和基质金属蛋白酶（MMP）2表达。我们的研究结果清楚地表明，辐射暴露显着延迟伤口愈合的剂量相关的方式。辐射和受伤的皮肤的评价显示减少沉积层粘连蛋白332蛋白在表皮基底膜连同所有三个层粘连蛋白332基因的表达升高postirradiation内3天。层粘连蛋白332基因表达的升高被MMP 2的基因和蛋白表达的升高所掩盖，这表明照射皮肤中层粘连蛋白332的量减少是由于层粘连蛋白332分泌与其通过升高的组织金属蛋白酶的加速加工之间的不平衡。培养的大鼠角质形成细胞的蛋白质印迹分析表明，减少层粘连蛋白332沉积的辐射细胞，和孵育的辐射角质形成细胞与MMP抑制剂显着增加沉积层粘连蛋白332的量。此外，辐射角质形成细胞表现出较长的时间来关闭人工伤口，这种延迟部分纠正接种角质形成细胞层粘连蛋白332包被板。这些数据有力地表明，层粘连蛋白332沉积被电离辐射抑制，并且与较慢的角质形成细胞迁移相结合，可以有助于辐射皮肤的延迟伤口愈合。(C)2011年，辐射研究学会
Jourdan, M. M., Lopez, A., Olasz, E. B., Duncan, N. E., Demara, M., Kittipongdaja, W., Fish, B. L., Mader, M., Schock, A., Morrow, N. V., Semenenko, V. A., Baker, J. E., Moulder, J. E. and Lazarova, Z. Laminin 332 Deposition is Diminished in Irradiated Skin in an Animal Model of Combined Radiation and Wound Skin Injury. Radiat. Res. 176, 636-648 (2011).Skin exposure to ionizing radiation affects the normal wound healing process and greatly impacts the prognosis of affected individuals. We investigated the effect of ionizing radiation on wound healing in a rat model of combined radiation and wound skin injury. Using a soft X-ray beam, a single dose of ionizing radiation (10-40 Gy) was delivered to the skin without significant exposure to internal organs. At 1 h postirradiation, two skin wounds were made on the back of each rat. Control and experimental animals were euthanized at 3, 7, 14, 21 and 30 days postirradiation. The wound areas were measured, and tissue samples were evaluated for laminin 332 and matrix metalloproteinase (MMP) 2 expression. Our results clearly demonstrate that radiation exposure significantly delayed wound healing in a dose-related manner. Evaluation of irradiated and wounded skin showed decreased deposition of laminin 332 protein in the epidermal basement membrane together with an elevated expression of all three laminin 332 genes within 3 days postirradiation. The elevated laminin 332 gene expression was paralleled by an elevated gene and protein expression of MMP2, suggesting that the reduced amount of laminin 332 in irradiated skin is due to an imbalance between laminin 332 secretion and its accelerated processing by elevated tissue metalloproteinases. Western blot analysis of cultured rat keratinocytes showed decreased laminin 332 deposition by irradiated cells, and incubation of irradiated keratinocytes with MMP inhibitor significantly increased the amount of deposited laminin 332. Furthermore, irradiated keratinocytes exhibited a longer time to close an artificial wound, and this delay was partially corrected by seeding keratinocytes on laminin 332-coated plates. These data strongly suggest that laminin 332 deposition is inhibited by ionizing radiation and, in combination with slower keratinocyte migration, can contribute to the delayed wound healing of irradiated skin. (C) 2011 by Radiation Research Society