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Am J Transl Res. 2019 Mar 15;11(3):1895-1907. eCollection 2019.

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

Zhou H1,2, Wei M3, Lu L1,2, Chu T4, Li X3, Fu Z3, Liu J1,2, Kang Y1,2, Liu L1,2, Lou Y1,2, Zhang C1,2, Gao Y5, Kong X6, Feng S1,2.

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Department of Orthopedics, Tianjin Medical University General Hospital No. 154 Anshan Road, Heping District, Tianjin 300052, PR China.
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.
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.
Kosair Children's Hospital Research Institute at The Department of Pediatrics, University of Louisville School of Medicine Louisville, Kentucky 40202, USA.
Department of Orthopedics, Henan Province People's Hospital Zhengzhou 450000, Henan, China.
School of Medicine, Nankai University No. 94 Weijin Road, Nankai District, Tianjin 300071, PR China.


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.


Ang-2; Neural stem cell; mTOR; neuronal differentiation; rapamycin


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