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Angiopoietin-2 induces the neuronal differentiation of mouse embryonic NSCs via phosphatidylinositol 3 kinase-Akt pathway-mediated phosphorylation of mTOR.

Authors
  • Zhou, Hengxing1, 2
  • Wei, Meng3
  • Lu, Lu1, 2
  • Chu, Tianci4
  • Li, Xueying3
  • Fu, Zheng3
  • Liu, Jun1, 2
  • Kang, Yi1, 2
  • Liu, Lu1, 2
  • Lou, Yongfu1, 2
  • Zhang, Chi1, 2
  • Gao, Yanzheng5
  • Kong, Xiaohong6
  • Feng, Shiqing1, 2
  • 1 Department of Orthopedics, Tianjin Medical University General Hospital No. 154 Anshan Road, Heping District, Tianjin 300052, PR China. , (China)
  • 2 Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair and Regeneration in The Central Nervous System, Ministry of Education Tianjin City, No. 154 Anshan Road, Heping District, Tianjin 300052, PR China. , (China)
  • 3 Key Laboratory of Immuno Microenvironment and Disease of The Educational Ministry of China, Department of Immunology, Tianjin Medical University No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. , (China)
  • 4 Kosair Children's Hospital Research Institute at The Department of Pediatrics, University of Louisville School of Medicine Louisville, Kentucky 40202, USA.
  • 5 Department of Orthopedics, Henan Province People's Hospital Zhengzhou 450000, Henan, China. , (China)
  • 6 School of Medicine, Nankai University No. 94 Weijin Road, Nankai District, Tianjin 300071, PR China. , (China)
Type
Published Article
Journal
American journal of translational research
Publisher
Madison, WI : e-Century Pub. Corp.
Publication Date
Jan 01, 2019
Volume
11
Issue
3
Pages
1895–1907
Identifiers
PMID: 30972213
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The fate of neural stem cells (NSCs) is decided by numerous growth factors. Among these factors, the well-known angiogenic factor angiopoietin-2 (Ang-2) has been revealed to participate in neurogenesis separate from its role in angiogenesis. However, the effect of Ang-2 on the fate determination of mouse embryonic NSCs and the underlying mechanism remain unclear. This result of this study indicated that treatment of mouse embryonic NSCs with 200 ng/ml Ang-2 significantly promoted neuronal differentiation without affecting glial differentiation, and mammalian target of rapamycin (mTOR) was phosphorylated in a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner during this process. Rapamycin, a specific mTOR inhibitor, suppressed the increase in neuronal differentiation stimulated by Ang-2, and this suppression did not result from an effect of Ang-2 or rapamycin on the apoptosis of differentiated NSCs. Collectively, our research demonstrates that PI3K/Akt pathway-mediated mTOR phosphorylation plays an important role in the Ang-2-enhanced neuronal differentiation of mouse embryonic NSCs.

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