Matrix Metalloproteinase-2 Is Involved in Myelination of Dorsal Root Ganglia Neurons
Matrix Metalloproteinase-2 Is Involved in Myelination of Dorsal Root Ganglia Neurons
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DOI：
10.1002/glia.20774
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发表时间：
2009-04-01
期刊：
影响因子：
6.2
通讯作者：
Kieseier, Bernd C.
中科院分区：
文献类型：
--
作者：
Lehmann, Helmar C.;Koehne, Angelika;Kieseier, Bernd C.
基质金属蛋白酶（MMP）包括能够降解所有细胞外基质组分的大家族的内肽酶。越来越多的证据表明，基质金属蛋白酶不仅参与组织破坏，但也可能发挥有益的作用，在轴突再生和神经髓鞘再生。在这里，我们提供的证据表明，MMP-2（明胶酶A）与周围神经系统（PNS）髓鞘形成的生理过程。在髓鞘化共同培养模型的雪旺细胞和背根神经节神经元，MMP-2的表达与髓鞘化的程度，通过免疫细胞化学，酶谱，免疫吸附测定。化学抑制剂对MMP-2活性的调节导致髓鞘形成不完全和异常。在体内MMP-2的表达检测脑脊液（CSF）的格林-巴利综合征患者，以及在CSF和腓肠神经活检的慢性炎症性脱髓鞘性多发性神经病患者。我们的研究结果表明，MMP-2在PNS髓鞘形成过程中的重要作用，以前未被认识。内源性或外源性调节MMP-2活性可能是促进PNS脱髓鞘疾病再生的相关靶点。(C)2008 Wiley-Liss，Inc.
Matrix metalloproteinases (MMPs) comprise a large family of endopeptidases that are capable of degrading all extracellular matrix components. There is increasing evidence that MMPs are not only involved in tissue destruction but may also exert beneficial effects during axonal regeneration and nerve remyelination. Here, we provide evidence that MMP-2 (gelatinase A) is associated with the physiological process of myelination in the peripheral nervous system (PNS). In a myelinating co-culture model of Schwann cells and dorsal root ganglia neurons, MMP-2 expression correlated with the degree of myelination as determined by immunocytochemistry, zymography, and immunosorbent assay. Modulation of MMP-2 activity by chemical inhibitors led to incomplete and aberrant myelin formation. In vivo MMP-2 expression was detected in the cerebrospinal fluid (CSF) of patients with Guillain-Barre syndrome as well as in CSF and sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy. Our findings suggest an important, previously unrecognized role for MMP-2 during myelination in the PNS. Endogenous or exogenous modulation of MMP-2 activity may be a relevant target to enhance regeneration in demyelinating diseases of the PNS. (C) 2008 Wiley-Liss, Inc.