Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells
Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells
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DOI：
10.1111/j.1471-4159.2006.03890.x
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发表时间：
2006-07-01
影响因子：
4.7
通讯作者：
Sakanaka, Masahiro
中科院分区：
文献类型：
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作者：
Cao, Fang;Hata, Ryuji;Sakanaka, Masahiro
为了研究细胞因子信号传导抑制因子3（SOCS 3）对神经干细胞命运的影响，用表达SOCS 3的腺病毒载体感染干细胞。3 d后，Western blot分析和免疫细胞化学分析显示，SOCS 3转染细胞中MAP 2蛋白水平和MAP 2阳性细胞数显著增加，而GFAP蛋白水平和GFAP阳性细胞数显著减少。此外，启动子分析显示，在转染细胞中的信号转导和转录激活因子3（Stat 3）的转录水平显着降低。此外，Notch家族成员（notch 1）和抑制性碱性螺旋-环-螺旋（bHLH）因子（hes 5和id 3）的mRNA水平在SOCS 3过表达后1天显著上调。转染后3天，hes 5的mRNA水平显著下降，而notch 1的mRNA水平仍在上调。此外，所有SOCS 3阳性细胞表达Nestin蛋白，但不表达MAP 2或GFAP蛋白。这些数据表明SOCS 3的过表达诱导神经干细胞中的神经发生并抑制星形胶质细胞的发生。我们的数据还表明SOCS 3促进神经干细胞的维持。
To investigate the effects of suppressors of cytokine signaling 3 (SOCS3) on neural stem cell fate, stem cells were infected with an adenoviral vector expressing SOCS3. Three days later, western blot analysis and immunocytochemical analysis revealed that the protein level of MAP2 and the number of MAP2-positive cells were significantly increased in SOCS3-transfected cells, whereas the protein level of GFAP and the number of GFAP-positive cells were significantly decreased. Furthermore, promoter assay revealed a significant reduction in the transcriptional level of signal transducer and activator of transcription 3 (Stat3) in the transfected cells. In addition, the mRNA levels of Notch family member (notch1) and inhibitory basic helix-loop-helix (bHLH) factors (hes5 and id3) were significantly up-regulated 1 day after overexpression of SOCS3. Three days after transfection, the mRNA level of hes5 was significantly decreased, whereas that of notch1 was still up-regulated. Moreover, all of SOCS3-positive cells expressed Nestin protein but did not express MAP2 or GFAP proteins. These data indicate that overexpression of SOCS3 induced neurogenesis and inhibited astrogliogenesis in neural stem cells. Our data also show that SOCS3 promoted maintenance of neural stem cells.