Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration
Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration
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DOI：
10.1016/j.expneurol.2013.01.025
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发表时间：
2013-09-01
影响因子：
5.3
通讯作者：
Schachner, Melitta
中科院分区：
文献类型：
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作者：
Akyuez, Nuray;Rost, Sandra;Schachner, Melitta
硫酸软骨素(CS)和硫酸皮肤素(DS)蛋白多糖是细胞外基质的主要成分，与神经发育、可塑性和再生有关。虽然CS被认为是神经再生的主要抑制因子，但DS对神经再生的贡献尚未得到评估。为了提供一种新的方法来研究DS和CS在发育和再生过程中的作用，我们培育了一只皮肤4-O-磺酸转移酶1(Chst14(-/-))缺陷的小鼠，Chst14(-/-)是合成DS而不是CS中含有艾杜糖酸的模块的关键酶。在野生型小鼠中，Chst14在皮肤和神经系统中高水平表达，并在星形胶质细胞和雪旺细胞中丰富。与野生型(Chst14(+/+))相比，切除Chst14和假设不能产生DS会导致体重减少、生育力降低、尾巴扭曲和皮肤脆性增加，但大脑重量和大体解剖没有受到影响。Chst14(-/-)小鼠的神经元和雪旺细胞在体外形成较长的突起，且Chst14(-/-)雪旺细胞的增殖高于Chst14(+/+)雪旺细胞。股神经切断/缝合后，Chst14(-/-)小鼠的功能恢复和轴突再生开始加快，但损伤后3个月的最终结果并不好于Chst14(+/+)小鼠。这些结果表明，虽然Chst14及其酶产物对神经发育的重要性有限，但它们可能对成年哺乳动物神经系统的再生限制环境起到了作用。(C)2013 Elsevier Inc.保留所有权利。
Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans are major components of the extracellular matrix implicated in neural development, plasticity and regeneration. While it is accepted that CS are major inhibitors of neural regeneration, the contributions of DS to regeneration have not been assessed. To enable a novel approach in studies on DS versus CS roles during development and regeneration, we generated a mouse deficient in the dermatan 4-O-sulfotransferase1 (Chst14(-/-)), a key enzyme in the synthesis of iduronic acid-containing modules found in DS but not CS. In wild-type mice, Chst14 is expressed at high levels in the skin and in the nervous system, and is enriched in astrocytes and Schwann cells. Ablation of Chst14, and the assumed failure to produce DS, resulted in smaller body mass, reduced fertility, kinked tail and increased skin fragility compared with wild-type (Chst14(+/+)) littermates, but brain weight and gross anatomy were unaffected. Neurons and Schwann cells from Chst14(-/-) mice formed longer processes in vitro, and Chst14(-/-) Schwann cells proliferated more than Chst14(+/+) Schwann cells. After femoral nerve transection/suture, functional recovery and axonal regrowth in Chst14(-/-) mice were initially accelerated but the final outcome 3 months after injury was not better than that in Chst14(+/+) littermates. These results suggest that while Chst14 and its enzymatic products might be of limited importance for neural development, they may contribute to the regeneration-restricting environment in the adult mammalian nervous system. (C) 2013 Elsevier Inc. All rights reserved.