Zhang Jing, Zhang Lu, Chen Yani, Shi Haiyan, Huang Xiaoyong, Wang Yanfeng, Wang Yu, Wei Yameng, Xue Wanjuan, Han Jiming
a Department of Clinical Medicine , Medical College of Yan'an University , Yan'an , P.R. China.
b Department of Foreign Languages , Ming De College of Northwestern Polytechnical University , Xi'an , P.R. China.
Biosci Biotechnol Biochem. 2019 Jun;83(6):1027-1034. doi: 10.1080/09168451.2019.1578639. Epub 2019 Feb 10.
Here, we investigated the effects and molecular mechanisms of metabotropic glutamate receptor 6 (mGluR6) on rat embryonic neural stem cells (NSCs). Overexpression of mGluR6 significantly promoted the proliferation of NSCs and increased the diameter of neutrospheres after treatment for 24 h, 48 h and 72 h. Overexpression of mGluR6 promoted G1 to S phase transition, with significantly decreased cell ratio in G1/G0 phase but significantly increased cell ratio in S phase. Additionally, mGluR6 overexpression for 48 h decreased the early and late apoptosis significantly. Moreover, overexpression of mGluR6 significantly increased the expression of p-ERK1/2, Cyclin D1 and CDK2, while the expression of p-p38 was significantly decreased. On the contrary, these effects of mGluR6 overexpression were reversed by mGluR6 knockdown. In conclusion, mGluR6 promotes the proliferation of NSCs by activation of ERK1/2-Cyclin D1/CDK2 signaling pathway and inhibits the apoptosis of NSCs by blockage of the p38 MAPK signaling pathway.
在此，我们研究了代谢型谷氨酸受体6（mGluR6）对大鼠胚胎神经干细胞（NSCs）的影响及其分子机制。mGluR6过表达在处理24小时、48小时和72小时后显著促进了神经干细胞的增殖，并增加了神经球的直径。mGluR6过表达促进了G1期到S期的转变，G1/G0期细胞比例显著降低，而S期细胞比例显著增加。此外，mGluR6过表达48小时可显著降低早期和晚期凋亡。而且，mGluR6过表达显著增加了p-ERK1/2、细胞周期蛋白D1和细胞周期蛋白依赖性激酶2（CDK2）的表达，而p-p38的表达显著降低。相反，mGluR6敲低可逆转mGluR6过表达的这些作用。总之，mGluR6通过激活ERK1/2-细胞周期蛋白D1/CDK2信号通路促进神经干细胞的增殖，并通过阻断p38丝裂原活化蛋白激酶（MAPK）信号通路抑制神经干细胞的凋亡。
