Recombinant insulin-like growth factor binding protein-4 inhibits proliferation and promotes differentiation of neural progenitor cells.
Insulin-like growth factor (IGF) is involved in regulating many processes during neural development, and IGF binding protein-4 (IGFBP4) functions as a modulator of IGF actions or in an IGF-independent manner (e.g., via inhibiting Wnt/β-catenin signaling). In the present study, neural progenitor cells (NPCs) were isolated from the forebrain of newborn mice to investigate effects of IGFBP4 on the proliferation and differentiation of NPCs. The proliferation of NPCs was evaluated using Cell Counting Kit-8 (CCK-8) after treatment with or without IGFBP4 as well as blockers of IGF-IR and β-catenin. Phosphorylation levels of Akt, Erk1, 2 and p38 were analyzed by Western blotting. The differentiation of NPCs was evaluated using immunofluorescence and Western blotting. It was shown that exogenous IGFBP4 significantly inhibited the proliferation of NPCs and it did not induce a more pronounced inhibition of cell proliferation after blockade of IGF-IR but it did after antagonism of β-catenin. Akt phosphorylation was significantly decreased and phosphorylation levels of Erk1, 2 and p38 were not significantly changed in IGFBP4-treated NPCs. Excessive IGFBP4 significantly promoted NPCs to differentiate into astrocytes and neurons. These data suggested that exogenous IGFBP4 inhibits proliferation and promotes differentiation of neural progenitor cells mainly through IGF-IR signaling pathway.
Department of Neurobiology, Beijing Center of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Laboratory of Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, 100069, China.
Hanxu
H
Niu
Department of Neurobiology, Beijing Center of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Laboratory of Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, 100069, China.
Rongbin
R
Gou
Department of Neurobiology, Beijing Center of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Laboratory of Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, 100069, China.
Qunyuan
Q
Xu
Department of Neurobiology, Beijing Center of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Laboratory of Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, 100069, China. Electronic address: duandy@ccmu.edu.cn.
Deyi
D
Duan
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018974:Insulin-Like Growth Factor Binding Protein 4; D051057:Proto-Oncogene Proteins c-akt; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
Cell proliferation; IGF-IR; IGFBP4; Neural differentiation; Neural progenitor cells