Gu Wen-Li, Fu Sai-Li, Wang Yan-Xia, Li Ying, Wang Xiao-Fei, Xu Xiao-Ming, Lu Pei-Hua
Department of Neurobiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Acta Pharmacol Sin. 2007 Oct;28(10):1519-30. doi: 10.1111/j.1745-7254.2007.00659.x.
To have a better understanding of the expression and regulation of versican isoforms in neural precursor cells (NPC) and oligodendrogliogenesis.
By immunocytochemistry, RT-PCR, and real-time PCR, we examined the temporal expression of versican in NPC isolated from embryonic d 16 rats as well as in oligodendrocyte (OL) lineage cells induced to differentiate from NPC, which mimicked the oligodendrogliogenesis in vivo.
We found that versican was constitutively expressed in NPC and their lineage cells, including neurons, astrocytes, and OL. In addition, 2 versican isoforms, V1/V0 and V2, were found to express at low levels in NPC, but at significantly higher levels in OL lineage cells. The peak expression of versican V2 was found at the oligodendrocyte precursor cell stage. Furthermore, the treatment of 2 pro-inflammatory cytokines, TNF-alpha and IFN-gamma, enhanced the transcription of versican V2 in NPC in a dose-dependent manner, but showed no effect on V1/V0 expression.
Taken together, our results demonstrate that versican, particularly the inhibitory V2 isoform, is increasingly expressed in OL lineage cells induced to differentiate from NPC. An increase in versican V2 expression after cytokine stimulation implies the interplay between the injury-induced upregulation of inflammatory cytokines and chondroitin sulfate proteoglycan-mediated inhibition of axonal regeneration after central nervous system injury.
更好地了解多功能蛋白聚糖异构体在神经前体细胞(NPC)及少突胶质细胞生成中的表达与调控。
通过免疫细胞化学、逆转录-聚合酶链反应(RT-PCR)及实时定量PCR,我们检测了从胚胎第16天大鼠分离出的NPC以及从NPC诱导分化而来的少突胶质细胞(OL)谱系细胞中多功能蛋白聚糖的时序表达,该过程模拟了体内少突胶质细胞生成。
我们发现多功能蛋白聚糖在NPC及其谱系细胞(包括神经元、星形胶质细胞和OL)中组成性表达。此外,发现两种多功能蛋白聚糖异构体V1/V0和V2在NPC中低水平表达,但在OL谱系细胞中表达水平显著更高。多功能蛋白聚糖V2的表达高峰出现在少突胶质前体细胞阶段。此外,两种促炎细胞因子肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)的处理以剂量依赖方式增强了NPC中多功能蛋白聚糖V2的转录,但对V1/V0表达无影响。
综上所述,我们的结果表明,多功能蛋白聚糖,尤其是抑制性异构体V2,在从NPC诱导分化而来的OL谱系细胞中表达逐渐增加。细胞因子刺激后多功能蛋白聚糖V2表达增加意味着损伤诱导的炎性细胞因子上调与硫酸软骨素蛋白聚糖介导的中枢神经系统损伤后轴突再生抑制之间存在相互作用。