IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway.
IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway.
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IGF-1通过PI3K/Akt途径促进神经干细胞Brn-4的表达和神经元分化。
DOI：
10.1371/journal.pone.0113801
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Jin G
中科院分区：
文献类型：
--
作者：
Zhang X;Zhang L;Cheng X;Guo Y;Sun X;Chen G;Li H;Li P;Lu X;Tian M;Qin J;Zhou H;Jin G
我们以前的研究表明，转录因子Brn-4上调手术去神经海马在体内，促进神经元分化的海马神经干细胞（NSCs）在体外。在失神经海马中介导Brn-4上调的分子仍然未知。在这项研究中，我们研究了胰岛素样生长因子-1（IGF-1）在海马去神经后的水平。手术去神经导致体内IGF-1表达显著增加。我们还报告说，IGF-1治疗在体外神经干细胞导致了显着加速的Brn-4的表达和细胞分化的神经元通路。PI 3 K特异性抑制剂（LY 294002）可阻断这种促进作用，但MAPK抑制剂（PD 98059）不能阻断这种作用; IGF-1处理可增加磷酸化Akt水平。此外，IGF-1受体（AG 1024）和mTOR（雷帕霉素）的抑制都减弱了IGF-1诱导的Brn-4表达增加。总之，结果表明，由海马去神经损伤诱导的IGF-1的上调导致PI 3 K/Akt信号通路的激活，这反过来又引起Brn-4的上调和随后的干细胞分化神经元通路。
Our previous studies indicated that transcription factor Brn-4 is upregulated in the surgically denervated hippocampus in vivo, promoting neuronal differentiation of hippocampal neural stem cells (NSCs) in vitro. The molecules mediating Brn-4 upregulation in the denervated hippocampus remain unknown. In this study we examined the levels of insulin-like growth factor-1 (IGF-1) in hippocampus following denervation. Surgical denervation led to a significant increase in IGF-1 expression in vivo. We also report that IGF-1 treatment on NSCs in vitro led to a marked acceleration of Brn-4 expression and cell differentiation down neuronal pathways. The promotion effects were blocked by PI3K-specific inhibitor (LY294002), but not MAPK inhibitor (PD98059); levels of phospho-Akt were increased by IGF-1 treatment. In addition, inhibition of IGF-1 receptor (AG1024) and mTOR (rapamycin) both attenuated the increased expression of Brn-4 induced by IGF-1. Together, the results demonstrated that upregulation of IGF-1 induced by hippocampal denervation injury leads to activation of the PI3K/Akt signaling pathway, which in turn gives rise to upregulation of the Brn-4 and subsequent stem cell differentiation down neuronal pathways.
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在两个人类神经干细胞系中神经元生理反应性的差异发展。
影响因子：
2.4
作者：
Donato, Roberta;Miljan, Erik A.;Hines, Susan J.;Aouabdi, Sihem;Pollock, Kenneth;Patel, Sara;Edwards, Frances A.;Sinden, John D.
通讯作者：
Sinden, John D.
DOI：
10.1523/jneurosci.6785-10.2011
发表时间：
2011-06-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kwon M;Fernández JR;Zegarek GF;Lo SB;Firestein BL
通讯作者：
Firestein BL
影响因子：
3.5
作者：
Luskin, MB;Zigova, T;Stewart, RR
通讯作者：
Stewart, RR
影响因子：
64.5
作者：
INGRAHAM, HA;CHEN, R;ROSENFELD, MG
通讯作者：
ROSENFELD, MG
影响因子：
5.3
作者：
Lin, Shuying;Fan, Lir-Wan;Rhodes, Philip G.;Cai, Zhengwei
通讯作者：
Cai, Zhengwei