Yanjie Jia, Jiping Sun, Yan Zhou, Xiaofeng Zhu, Boai Zhang, Yajun Lian
Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Neuroreport. 2007 Sep 17;18(14):1443-7. doi: 10.1097/WNR.0b013e3282ef7753.
In this study, the putative involvement of the Notch-1 signaling pathway in the neuronal differentiation of bone marrow mesenchymal stem cells (BMSCs) was investigated through RNA interference (RNAi). We found that mNotch-1shRNA could efficiently block expression of Notch-1 in BMSCs. After induction, immunohistochemistry, reverse transcriptase-PCR and Western blot analyses, all indicated that the expression of neuron-specific markers such as neuron-specific enolase and neurofilament 200 was much higher in mNotch-1shRNA BMSCs than that in control groups, whereas the expression of glial fibrillary acidic protein was lower in mNotch-1shRNA BMSCs. The percentage of apoptotic cells in mNotch-1shRNA BMSCs, however, was significantly higher than that in control groups. These data indicate that Notch signaling plays a role in the differentiation of BMSCs into neurons in vitro. Pharmacological or genetic interference with Notch signaling may provide a novel method to obtain neurons for therapeutic use.
在本研究中,通过RNA干扰(RNAi)研究了Notch-1信号通路在骨髓间充质干细胞(BMSCs)神经元分化中的假定作用。我们发现mNotch-1shRNA能够有效阻断BMSCs中Notch-1的表达。诱导后,免疫组织化学、逆转录聚合酶链反应和蛋白质免疫印迹分析均表明,与对照组相比,mNotch-1shRNA BMSCs中神经元特异性烯醇化酶和神经丝200等神经元特异性标志物的表达要高得多,而mNotch-1shRNA BMSCs中胶质纤维酸性蛋白的表达则较低。然而,mNotch-1shRNA BMSCs中凋亡细胞的百分比明显高于对照组。这些数据表明Notch信号在体外BMSCs向神经元的分化中发挥作用。对Notch信号进行药理学或基因干扰可能为获得用于治疗的神经元提供一种新方法。