Suppression of Nestin reveals a critical role for p38-EGFR pathway in neural progenitor cell proliferation

The expression of intermediate filament Nestin is necessary for the neural progenitor cells (NPCs) to maintain stemness, but the underlying cellular and molecular mechanism remains unclear. In this study, we demonstrated that Nestin is required for the self-renew of NPCs through activating MAPK and...

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Bibliographic Details
Published in:Oncotarget 2016-12, Vol.7 (52), p.87052-87063
Main Authors: Hu, Wentao, Lu, Hong, Wang, Shang, Yin, Wenhan, Liu, Xujie, Dong, Lin, Chiu, Richard, Shen, Li, Lu, Wen-Jing, Lan, Feng
Format: Article
Language:English
Subjects:
Animals
Cell Cycle Checkpoints
Cell Differentiation
Cell Proliferation
Imidazoles - pharmacology
Mice
Nestin - antagonists & inhibitors
Nestin - physiology
Neural Stem Cells - cytology
Neural Stem Cells - physiology
p38 Mitogen-Activated Protein Kinases - physiology
Receptor, Epidermal Growth Factor - physiology
Research Paper
RNA, Small Interfering - genetics
Signal Transduction - physiology
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Summary:The expression of intermediate filament Nestin is necessary for the neural progenitor cells (NPCs) to maintain stemness, but the underlying cellular and molecular mechanism remains unclear. In this study, we demonstrated that Nestin is required for the self-renew of NPCs through activating MAPK and EGFR pathways. Knockdown of Nestin by shRNA inhibited cell cycle progression and proliferation in mouse NPCs. Moreover, suppression of Nestin reduced expression of the epidermal growth factor receptor (EGFR) in NPCs and inhibited the mitogenic effects of EGF on these cells. Treatment of NPCs with p38-MAPK inhibitor PD169316 reversed cell cycle arrest caused by the knockdown of Nestin. Our findings indicate that Nestin promotes NPC proliferation via p38-MAPK and EGFR pathways, and reveals the necessity of these pathways in NPCs self-renewal.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.13498