ADAM8 is selectively up-regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice.
ADAM8 is selectively up-regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice.
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DOI：
10.1002/cne.21902
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发表时间：
2009-01-10
影响因子：
2.5
通讯作者：
Hagg, Theo
中科院分区：
文献类型：
--
作者：
Mahoney, Edward T.;Benton, Richard L.;Maddie, Melissa A.;Whittemore, Scott R.;Hagg, Theo
关键词：
脊髓损伤 (SCI) 后第一周内会发生内皮细胞 (EC) 损失和随后的血管生成。为了确定静脉 (i.v) 治疗的分子机制，我们确定了跨膜 A 解整合素和金属蛋白酶 (ADAM) 蛋白是否在受损脊髓的 EC 中表达。 ADAM 与整合素结合，这对于 EC 存活和血管生成很重要。脊髓挫伤的雌性成年 C57Bl/6 小鼠在受伤后 1 至 28 天之间，血管和个体 EC 中的 ADAM8 (CD156) 免疫染色逐渐增多。未受伤的脊髓几乎没有 ADAM8 染色。 ADAM8 mRNA 和蛋白质的增加在脊髓裂解物中得到证实，并且 ADAM8 mRNA 存在于富含 FACS 的 EC 中。 ADAM8 与 EC 标记 PECAM 以及 i.v. 广泛且排他地共定位。注射凝集素。静脉注射损伤后 3-7 天，注射异凝集素 B4 (IB4) 标记损伤中心及其内的血管亚群，与血管生成同时发生。 ADAM8 和增殖标记物 Ki-67 均存在于 IB4 阳性微血管中。在IB4阳性血管的前端观察到ADAM8阳性增殖细胞。通过 BrdU 掺入、静脉注射结合证实血管生成。注射核仁素抗体，并对部分血管进行 MT1-MMP 免疫染色。这些数据表明 ADAM8 具有血管选择性，并且在 SCI 后血管生成过程中 EC 的增殖和/或迁移中发挥作用。
Endothelial cell (EC) loss and subsequent angiogenesis occurs over the first week after spinal cord injury (SCI). To identify molecular mechanisms that could be targeted with intravenous (i.v.) treatments we determined whether transmembrane A Disintegrin And Metalloprotease (ADAM) proteins are expressed in ECs of the injured spinal cord. ADAMs bind to integrins which are important for EC survival and angiogenesis. Female adult C57Bl/6 mice with a spinal cord contusion had progressively more ADAM8 (CD156) immunostaining in blood vessels and individual ECs between 1 and 28 days following injury. Uninjured spinal cords had little ADAM8 staining. The increase in ADAM8 mRNA and protein was confirmed in spinal cord lysates, and ADAM8 mRNA was present in FACS-enriched ECs. ADAM8 co-localized extensively and exclusively with the EC marker PECAM and also with i.v. injected lectins. I.v. injected isolectin B4 (IB4) labels a subpopulation of blood vessels at and within the injury epicenter 3-7 days after injury, coincident with angiogenesis. Both ADAM8 and the proliferation marker Ki-67 were present in IB4-positive microvessels. ADAM8-positive proliferating cells were seen at the leading end of IB4-positive blood vessels. Angiogenesis was confirmed by BrdU incorporation, binding of i.v. injected nucleolin antibodies, and MT1-MMP immunostaining in a subset of blood vessels. These data suggest that ADAM8 is vascular-selective and plays a role in proliferation and/or migration of ECs during angiogenesis following SCI.
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影响因子：
2.5
作者：
Benton, Richard L.;Maddie, Melissa A.;Whittemore, Scott R.
通讯作者：
Whittemore, Scott R.
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
6.2
作者：
Goddard, DR;Bunning, RAD;Woodroofe, MN
通讯作者：
Woodroofe, MN
影响因子：
5.3
作者：
Casella, GTB;Marcillo, A;Wood, PM
通讯作者：
Wood, PM