Ectopic expression of angiopoietin-1 promotes neuronal differentiation in neural progenitor cells through the Akt pathway.
In regions of adult neurogenesis, neural progenitor cells (NPCs) are found in close proximity to blood vessels within a so-called 'vascular niche'. Neurogenesis is linked to angiogenesis via certain growth factors. We propose that angiopoietin-1 (Ang1), which is similar to VEGF, has a unique role in neurogenesis independent of its role in angiogenesis. In this study, primary cultures of NPCs were transduced with recombinant adenoviruses expressing Ang1 and induced to differentiate with dibutyryl cyclic AMP (dbcAMP). Neuronal differentiation was evaluated by quantitative PCR, immunofluorescence microscopy and Western blot analysis. The results show that ectopic expression of Ang1 promotes neuronal differentiation and neurite outgrowth in NPCs, while this effect was blocked by the presence of anti-Tie2 receptor antibody or the PI3-K inhibitor, LY294002. Our results suggest that Ang1, identified originally as an angiogenic factor, can also stimulate in vitro neurogenesis in NPCs through the Akt pathway.
Bai
Yun
Y
Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian, Beijing 100191, China.
Cui
Ming
M
Meng
Zhijun
Z
Shen
Li
L
He
Qihua
Q
Zhang
Xiaoyan
X
Chen
Fengrong
F
Xiao
Junjun
J
D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D042683:Angiopoietin-1; D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003994:Bucladesine; D042787:Receptor, TIE-2; D051057:Proto-Oncogene Proteins c-akt