IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway.
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...
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doaj-0a8696c9fde04ecc9daecb0d3a36305d2020-11-25T02:45:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11380110.1371/journal.pone.0113801IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway.Xinhua ZhangLei ZhangXiang ChengYuxiu GuoXiaohui SunGeng ChenHaoming LiPengcheng LiXiaohui LuMeiling TianJianbing QinHui ZhouGuohua JinOur 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.http://europepmc.org/articles/PMC4256305?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xinhua Zhang Lei Zhang Xiang Cheng Yuxiu Guo Xiaohui Sun Geng Chen Haoming Li Pengcheng Li Xiaohui Lu Meiling Tian Jianbing Qin Hui Zhou Guohua Jin |
spellingShingle |
Xinhua Zhang Lei Zhang Xiang Cheng Yuxiu Guo Xiaohui Sun Geng Chen Haoming Li Pengcheng Li Xiaohui Lu Meiling Tian Jianbing Qin Hui Zhou Guohua Jin IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway. PLoS ONE |
author_facet |
Xinhua Zhang Lei Zhang Xiang Cheng Yuxiu Guo Xiaohui Sun Geng Chen Haoming Li Pengcheng Li Xiaohui Lu Meiling Tian Jianbing Qin Hui Zhou Guohua Jin |
author_sort |
Xinhua Zhang |
title |
IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway. |
title_short |
IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway. |
title_full |
IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway. |
title_fullStr |
IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway. |
title_full_unstemmed |
IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway. |
title_sort |
igf-1 promotes brn-4 expression and neuronal differentiation of neural stem cells via the pi3k/akt pathway. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4256305?pdf=render |
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