Vascular MMP-9/TIMP-2 and Neuronal MMP-10 Up-Regulation in Human Brain after Stroke: A Combined Laser Microdissection and Protein Array Study

Vascular MMP-9/TIMP-2 and Neuronal MMP-10 Up-Regulation in Human Brain after Stroke: A Combined Laser Microdissection and Protein Array Study
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DOI:
10.1021/pr801012x
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发表时间:
2009-06-01
影响因子:
4.4
通讯作者:
Montaner, Joan
Montaner, Joan
中科院分区:
生物学2区
文献类型:
--
作者:
Cuadrado, Eloy;Rosell, Anna;Montaner, Joan

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基质金属蛋白酶(MMPs)在缺血性脑卒中后的脑损伤中起重要作用。在本研究中,我们的目的是评估MMP-家族蛋白质的全球表达在人类脑卒中后,通过使用探照灯蛋白阵列和激光显微切割相结合,以确定其细胞来源。该研究表明,与健康对照区域相比,MMP-1、MMP-2、MMP-3、MMP-8、MMP-9、MMP-10、MMP-13和TIMP-1在梗死组织中上调。使用激光显微切割,我们获得了特定的神经元和血管人口从梗死和对照区。从这些组分中,我们发现MMP-9和TIMP-2在脑微血管中高度产生,而MMP-10在缺血性脑的神经元中显著增加,但在健康区域中不增加。这些发现证明了选择性细胞依赖性MMP分泌,开辟了选择性靶向特定MMP用于中风后神经保护或血管保护的可能性。
Matrix Metalloproteinases (MMPs) play an important role in brain injury after ischemic stroke. In the present study, we aimed to assess the global expression of MMP-Family proteins in the human brain after stroke by using a combination of Searchlight Protein Array and Laser Microdissection to determine their cellular origin. This study demonstrated that MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-1 were upregulated in the infarcted tissue compared to healthy control areas. Using laser microdissection we obtained specific neuronal and vascular populations from both infarcted and control areas. From these fractions, we showed that MMP-9 and TIMP-2 were highly produced in brain microvessels while MMP-10 was notably increased in neurons of the ischemic brain but not in healthy areas. These findings demonstrate a selective cell-dependent MMP secretion, opening the possibility of selectively targeting specific MMPs for neuroprotection or vasculoprotection following stroke.