MMP-related gelatinase activity is strongly induced in scar tissue of injured adult spinal cord and forms pathways for ingrowing neurites
MMP-related gelatinase activity is strongly induced in scar tissue of injured adult spinal cord and forms pathways for ingrowing neurites
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DOI：
10.1006/mcne.2001.0986
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发表时间：
2001-06-01
影响因子：
3.5
通讯作者：
Stettler, O
中科院分区：
文献类型：
--
作者：
Duchossoy, Y;Horvat, JC;Stettler, O
成人脊髓半切后瘢痕形成伴随着周围细胞外基质（ECM）的重要重塑。由于ECM分子提供轴突生长的底物，ECM组成的这些变化可能会影响轴突再生的过程。在这里，我们研究了瘢痕形成是否与基质金属蛋白酶（MMPs）的激活有关，MMPs是一类参与ECM重塑的蛋白质，被认为有利于周围神经系统的轴突再生。发现MMP家族的两个成员MMP-2和MMP-9在SC伤口中瞬时上调。原位荧光酶谱显示MMP相关的明胶酶活性（GA）在伤口，这是空间和时间相关的瘢痕形成。GA形成了一个引人注目的交织路径模式，可以看到神经突沿着这些路径沿着生长。这些途径对应于其他ECM分子的分布，已知这些ECM分子对轴突再生具有拮抗作用。我们的研究结果表明，神经突长入伤口可能会暂时受益于ECM重塑，特别是MMP的上调。
Scar formation following adult spinal cord (SC) hemisection is accompanied by important remodeling of the surrounding extracellular matrix (ECM). Since ECM molecules provide the substrate for axon growth, these changes in ECM composition are likely to influence the process of axonal regeneration. Here we investigated whether scar formation could be associated with the activation of matrix metalloproteinases (MMPs), a class of proteins implicated in ECM remodeling thought to favor axonal regeneration in the peripheral nervous system. Two members of the MMP family, MMP-2 and MMP-9, were found to be transiently upregulated in the SC wound. In situ fluorescent zymography revealed a MMP-related gelatinase activity (GA) in the wound, which was spatially and temporally correlated with scar formation. The GA formed a striking pattern of interwoven pathways along which neurites were seen to grow. These pathways corresponded to the distribution of other ECM molecules, which are known to have antagonistic effects on axonal regrowth. Our results suggest that neurite ingrowth into the wound may transiently benefit from this ECM remodeling and, in particular, from the upregulation of MMPs.