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王雅楠, 杨觅, 余丽华等. 瘦素对STAT3信号的调节在小鼠神经干细胞向星形胶质细胞分化中的作用[J]. koko体育app 学报(医学版), 2014, 45(4): 552-556.
引用本文: 王雅楠, 杨觅, 余丽华等. 瘦素对STAT3数据信号的调节器在小鼠周围神经干神经组织细胞向星形胶质神经组织细胞分解中的帮助[J]. 上海一本大学学报(临床医学版), 2014, 45(4): 552-556.
WANG Ya-nan, YANG Mi, YU Li-hua. et al. Leptin Play the Key Role in Astroglial Differentiation of Mouse Neural Stem Cells and Regulated the STAT3 Signaling Through Jak-STAT3 Pathway[J]. Journal of Sichuan University (Medical Sciences), 2014, 45(4): 552-556.
Citation: WANG Ya-nan, YANG Mi, YU Li-hua. et al. Leptin Play the Key Role in Astroglial Differentiation of Mouse Neural Stem Cells and Regulated the STAT3 Signaling Through Jak-STAT3 Pathway[J]. Journal of Sichuan University (Medical Sciences), 2014, 45(4): 552-556.

瘦素对STAT3信号的调节在小鼠神经干细胞向星形胶质细胞分化中的作用

Leptin Play the Key Role in Astroglial Differentiation of Mouse Neural Stem Cells and Regulated the STAT3 Signaling Through Jak-STAT3 Pathway

  • 摘要: 目的 研究瘦素(Leptin)对神经干细胞的诱导分化作用并分析其分子机制。 方法 将胚胎小鼠神经干细胞与Leptin共培养,设立Leptin浓度梯度(0、0.05、0.2、0.5、1、2 mg/L),分析Leptin对神经干细胞的诱导分化作用,并用Janus蛋白酪氨酸激酶2/信号转导和转录激活子3(Jak-STAT3)信号通路与磷脂酰肌醇3激酶/蛋白激酶B (PI3k-Akt)信号通路抑制剂(10 μmol/L)处理细胞,利用Western blot及免疫荧光检测下游蛋白分子非磷酸化STAT3、磷酸化STAT3、非磷酸化Akt、磷酸化Akt及星形胶质细胞标记物胶质纤维酸性蛋白(GFAP)的表达。 结果 荧光免疫显示2 mg/L Leptin组80%表达GFAP,Western blot分析发现0.5、1、2 mg/L Leptin组GFAP的表达较0 mg/L Leptin组增加(P<0.05)。与0 h相比,2 mg/L Leptin共培养后24 h后GFAP表达开始随时间增长而增加,7 d达高峰(P<0.05)。加入STAT3抑制剂的神经干细胞磷酸化STAT3表达减少,GFAP表达减少;加入Akt抑制剂的神经干细胞,磷酸化Akt表达量减少,但GFAP表达量未减少。 结论 Leptin或可通过激活STAT3而非活化PI3k-Akt信号通路,诱导神经干细胞向星形胶质细胞分化。  
    Abstract: Objective To investigate the effect of Leptin on differentiation of nueral stem cell and explore the underline molecular mechanism. Methods Co-culture neural stem cell with different concentration of Leptin (0, 0.05, 0.2, 0.5, 1, 2 mg/L), the effect of Leptin on differentiation of nueral stem cell was analyzed. After treated the nueral stem cell with inhibitors of Jak-STAT3 〔Janus family tyrosine kinases (Jak kinases) and signal transducers and activators of transcription (STAT proteins) 〕and PI3k-Akt 〔phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)〕, the STAT3, phosphorylated-STAT3, Akt, phosphorylated-Akt levels and GFAP were detected with western blot and fluoroimmunoassay respectively. Results Morphology observation found nueral stem cell to change to astrocyte. An increased astrocyte marker (GFAP) in Leptin group but not Tuj-1 or MBP with fluoroimmunoassay and western blot detection was observed. The expression of GFAP began at 24 h after co-culture, and increased consistent with the concentration of Leptin. Jak-STAT3 inhibitors but not PI3k-Akt inhibitors decreased the expression of phosphorylated-STAT3, and accompanily decreased the expression of GFAP. Conclusion Leptin may have an effect on the astroglial differentiation on neural stem cells through the JAK-STAT3 pathway but not PI3k-Akt pathway.  
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