G protein-coupled estrogen receptor 1 negatively regulates the proliferation of mouse-derived neural stem/progenitor cells via extracellular signal-regulated kinase pathway
G protein-coupled estrogen receptor 1 negatively regulates the proliferation of mouse-derived neural stem/progenitor cells via extracellular signal-regulated kinase pathway
复制标题
G蛋白偶联雌激素受体1通过细胞外信号调节激酶途径负调节小鼠源性神经干/祖细胞的增殖
DOI：
10.1016/j.brainres.2019.02.024
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发表时间：
2019-07-01
期刊：
影响因子：
2.9
通讯作者：
Hu, Rong
中科院分区：
文献类型：
--
作者：
Zhong, Jun;Ge, Hong-fei;Hu, Rong
G蛋白偶联雌激素受体1（GPER 1，GPR 30）在中枢神经系统（CNS）中具有广泛的功能。然而，GPER 1是否由神经干/祖细胞（NSPCs）表达及其作用尚未确定。在此，我们通过免疫印迹和免疫荧光染色发现GPER 1在小鼠来源的NSPCs中表达。此外，我们发现，GPER 1的激动剂G1的特异性激活以剂量依赖的方式降低了NSPCs的增殖。神经球形成实验和Ki 67染色进一步证明GPER 1的激活抑制了NSPCs的增殖。GPER 1特异性拮抗剂G15可阻断G1对NSPCs增殖的抑制作用。GPER 1对NSPCs增殖的抑制作用可能与ERK信号通路有关，GPER 1可使NSPCs中ERK的磷酸化水平显著降低。而拮抗剂G15可逆转p-ERK的下调水平。敲低GPER 1也逆转了G1对NSPCs增殖的抑制作用。总之，我们的研究结果提供了第一个证据表明，GPER 1是由NSPCs表达，其激活负调节NSPCs的增殖，突出了GPER 1在调节NSPC行为的重要性。
G protein-coupled estrogen receptor 1 (GPER1, also known as GPR30) has been reported to play a wide range of function in the central nervous system (CNS). However, whether GPER1 is expressed by neural stem/progenitor cells (NSPCs) and its role has not been established. Here, we found the expression of GPER1 in mouse-derived NSPCs via western blot and immunofluorescent staining. Moreover, we revealed that specific activation of GPER1 by the agonist G1 decreased the proliferation of NSPCs in a dose-dependent manner. The neurosphere formation assay and Ki67 staining further demonstrated that activation of GPER1 inhibited the proliferation of NSPCs. Additionally, the inhibitory effect of G1 on the proliferation of NSPCs could be blocked by the specific GPER1 antagonist G15. Intriguingly, ERK pathway was involved in the negative effect of GPER1 on the proliferation of NSPCs, because the phosphorylation level of ERK in NSPCs was remarkably decreased during G1 treatment. However, the antagonist G15 reversed the down-regulated level of p-ERK. Knock-down GPER1 also reversed the inhibitory effect of G1 on NSPCs proliferation. Together, our results provide the first evidence that GPER1 is expressed by NSPCs and its activation negatively modulates the proliferation of NSPCs, highlighting the importance of GPER1 in regulating NSPC behaviors.