Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation
Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation
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神经胶质细胞以及正常和受损中枢神经系统中的硫酸乙酰肝素蛋白聚糖：磺基转移酶的表达和硫酸化的变化
DOI：
10.1111/j.1460-9568.2008.06042.x
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发表时间：
2008
影响因子：
3.4
通讯作者：
J. Fawcett
中科院分区：
文献类型：
--
作者：
F. Properzi;R. Lin;Jessica C. F. Kwok;M. Naidu;T. V. van Kuppevelt;G. T. ten Dam;L. M. Camargo;R. Raha;Yoko Furukawa;T. Mikami;K. Sugahara;J. Fawcett
硫酸乙酰肝素蛋白聚糖（HSPG）具有与CNS损伤反应的控制相关的多种功能，特别是在调节生长因子的作用和定位影响轴突生长的分子方面。我们研究了在正常和受损的中枢神经系统，星形胶质细胞和少突胶质细胞的前体，因为他们参与损伤反应的表达和糖化的HSPGs的模式。通过生化分析和识别硫酸化表位的抗体结合分析HS糖胺聚糖（GAG）链的组成。我们还测量了HS磺基转移酶和多配体聚糖的水平。与少突胶质细胞相比，少突胶质细胞前体在其HS GAG中具有更多的2-O-硫酸化。这伴随着负责2-O-硫酸化的酶HS 2-O-磺基转移酶（HS 2ST）的更高表达和syndecan-1的下降。用肿瘤生长因子（TGF）α或TGFβ处理以模拟损伤反应的星形胶质细胞显示syndecan-1和HS 2ST的上调与其HS GAG中2-O-硫酸酯残基的增加相关。这也与识别高硫酸化的AO 4 B 08抗GAG抗体染色增加和识别低硫酸化的RB 4 EA 12染色减少相关。成年大鼠脑损伤后，损伤部位周围HSPG的数量总体增加，HS 2ST的mRNA增加，硫酸化特异性抗体染色的变化与2-O-硫酸化HS的增加一致。Syndecan-1在星形胶质细胞中上调。在损伤的脑和培养的神经胶质细胞中观察到的主要损伤相关变化是2-O-硫酸化HS的增加和syndecan-1的增加，这表明了调节瘢痕形成的新方法。
Heparan sulphate proteoglycans (HSPGs) have multiple functions relevant to the control of the CNS injury response, particularly in modulating the effects of growth factors and localizing molecules that affect axon growth. We examined the pattern of expression and glycanation of HSPGs in the normal and damaged CNS, and in astrocytes and oligodendrocyte precursors because of their participation in the injury reaction. The composition of HS glycosaminoglycan (GAG) chains was analysed by biochemical analysis and by the binding of antibodies that recognize sulphated epitopes. We also measured levels of HS sulphotransferases and syndecans. Compared with oligodendrocytes, oligodendrocyte precursors have more 2‐O‐sulphation in their HS GAG. This is accompanied by higher expression of the enzyme responsible for 2‐O‐sulphation, HS 2‐O‐sulphotransferase (HS2ST) and a fall in syndecan‐1. Astrocytes treated with tumour growth factor (TGF)α or TGFβ to mimic the injury response showed upregulation of syndecan‐1 and HS2ST correlating with an increase in 2‐O‐sulphate residues in their HS GAGs. This also correlated with increased staining with AO4B08 anti‐GAG antibody that recognizes high sulphation, and reduced staining with RB4EA12 recognizing low sulphation. After injury to the adult rat brain there was an overall increase in the quantity of HSPG around the injury site, mRNA for HS2ST was increased, and the changes in staining with sulphation‐specific antibodies were consistent with an increase in 2‐O‐sulphated HS. Syndecan‐1 was upregulated in astrocytes. The major injury‐related change, seen in injured brain and cultured glia, was an increase in 2‐O‐sulphated HS and increased syndecan‐1, suggesting novel approaches to modulating scar formation.
DOI：
10.2741/1325
发表时间：
2004-05
期刊：
Frontiers in bioscience : a journal and virtual library
影响因子：
--
作者：
F. Irie;Yu Yamaguchi
通讯作者：
F. Irie;Yu Yamaguchi
多配体的发育表达：可能的功能和调节。
DOI：
--
发表时间：
1993
期刊：
Development (Cambridge, England). Supplement
影响因子：
--
作者：
Bernfield,M;Hinkes,MT;Gallo,RL
通讯作者：
Gallo,RL
硫酸乙酰肝素-生长因子的相互作用。
影响因子：
--
作者：
Rapraeger,AlanC
通讯作者：
Rapraeger,AlanC