Gliosis-specific transcription factor OASIS coincides with proteoglycan core protein genes in the glial scar and inhibits neurite outgrowth
Gliosis-specific transcription factor OASIS coincides with proteoglycan core protein genes in the glial scar and inhibits neurite outgrowth
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DOI：
10.2220/biomedres.33.345
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发表时间：
2012-12-01
影响因子：
1.2
通讯作者：
Tase, Choichiro
中科院分区：
文献类型：
--
作者：
Iseki, Ken;Hagino, Seita;Tase, Choichiro
OASIS 基因是 CREB/ATF 转录因子家族的成员，在中枢神经系统损伤后神经胶质增生中表达上调。然而，OASIS 如何参与神经胶质细胞反应仍有待确定。在神经胶质疤痕中，硫酸软骨素蛋白聚糖（CSPG）也会上调，从而抑制轴突再生。我们研究了 OASIS 在神经胶质增生中与 CSPG 核心蛋白相关的功能作用，这些蛋白使得病变不允许轴突再生。我们首先使用冷冻损伤小鼠大脑中的几种标记物检查了 OASIS 的基因表达定位，并通过双标记原位杂交将 CSPG 核心蛋白基因的表达模式与神经胶质疤痕中的 OASIS 的表达模式进行了比较。我们的研究结果表明，OASIS 在近端反应性星形胶质细胞中被诱导，这些星形胶质细胞表现出 CSPG 表达上调，包括 NG2 蛋白聚糖、多功能蛋白聚糖、短蛋白聚糖、神经蛋白聚糖和磷酸聚糖核心。此外，源自OASIS转染的C6细胞的膜组分抑制NG108-15细胞的神经突生长，而其神经突生长抑制作用在软骨素酶ABC处理后被消除。 OASIS 可能参与轴突生长的非许可环境的调节机制。
OASIS gene, a member of the CREB/ATF transcription factor family, is upregulated in gliosis after CNS injury. However it remains to be determined how OASIS is implicated in gliotic reaction. In a glial scar, chondroitin sulfate proteoglycans (CSPGs) are also upregulated, which engenders the inhibition of axonal regeneration. We investigated the functional role of OASIS in gliosis in relation to CSPG core proteins that render lesions non-permissive for regenerating axons. We first examined the gene expression localization of OASIS using several markers in a cryo-injured mouse brain and compared the expression pattern of CSPG core protein genes with that of OASIS in a glial scar by double-labeling in situ hybridization. Our findings suggest that OASIS is induced in proximal reactive astrocytes that exhibit upregulated expression for CSPGs, including NG2 proteoglycan, versican, brevican, neurocan, and phosphacan core. Furthermore, the membrane fraction derived from OASIS-transfected C6 cells inhibits neurite outgrowth of NG108-15 cells, whereas its neurite outgrowth inhibitory effect is abrogated after chondroitinase ABC treatment. OASIS is likely to be involved in the regulatory mechanism of non-permissive environments for axonal outgrowth.