Matrix metalloproteases: degradation of the inhibitory environment of the transected optic nerve and the scar by regenerating axons
Matrix metalloproteases: degradation of the inhibitory environment of the transected optic nerve and the scar by regenerating axons
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DOI：
10.1016/j.mcn.2004.08.013
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发表时间：
2005-01-01
影响因子：
3.5
通讯作者：
Logan, A
中科院分区：
文献类型：
--
作者：
Ahmed, Z;Dent, RG;Logan, A
中枢神经系统损伤后，损伤部位形成胶质/胶原疤痕，被认为是再生轴突的物理化学屏障。我们已经证明，当轴突的旺盛生长被刺激时，横断性视神经(ON)中的瘢痕形成被减弱。基质金属蛋白酶(MMPs)受基质金属蛋白酶组织抑制因子(TIMP)的调节，可降解多种细胞外基质成分(ECM)，并可被生长的轴突激活以重塑ECM，从而通过胶质或胶原瘢痕的抑制环境再生。在这里，我们研究了在体内无再生(瘢痕形成)和再生(无瘢痕)损伤模型中，基质金属蛋白酶水平是否受到调节。Western blotting和免疫组织化学结果显示，视网膜再生时，基质金属蛋白酶-1、-2和-9的表达水平高于未再生的视网膜，而TIMP-1和TIMP-2的表达水平低于未再生的视网膜和视网膜。原位酶谱显示再生模型的明胶酶活性明显增强，主要分布于残肢近端和病变周围的星形胶质细胞。这些结果表明，基质金属蛋白酶的激活和TIMP的同时下调可能减轻了再生过程中的抑制性瘢痕形成，从而将ON转化为轴突再生的非抑制性途径。(C)2004 Elsevier Inc.保留所有权利。
After injury to the central nervous system, a glial/collagen scar forms at the lesion site, which is thought to act as a physicochemical barrier to regenerating axons. We have shown that scar formation in the transected optic nerve (ON) is attenuated when robust growth of axons is stimulated. Matrix metalloproteases (MMP), modulated by tissue inhibitors of MMP (TIMP), degrade a wide variety of extracellular matrix components (ECM) and may be activated by growing axons to remodel the ECM to allow regeneration through the inhibitory environment of the glial or collagen scar. Here, we investigate whether MMP levels are modulated in a nonregenerating (scarring) versus a regenerating (nonscarring) model of ON injury in vivo. Western blotting and immunohistochemistry revealed that MMP-1, -2, and -9 levels were higher and TIMP-1 and TIMP-2 levels were lower in regenerating compared to nonregenerating ON and retinae. In situ zymography demonstrated significantly greater MMP-related gelatinase activity in the regenerating model, mainly colocalized to astrocytes in the proximal ON stump and around the lesion site. These results suggest that activation of MMP and coincident down-regulation of TIMP may act to attenuate the inhibitory scarring in the regenerating ON, thus transforming the ON into a noninhibitory pathway for axon regrowth. (C) 2004 Elsevier Inc. All rights reserved.