Original Paper

Neurochemical Research

, Volume 36, Issue 3, pp 406-411

First online:

IGFBP-3 Inhibits the Proliferation of Neural Progenitor Cells

  • Haviryaji S. G. KalluriAffiliated withDepartment of Neurosurgery, University of Wisconsin Email author 
  • , Robert J. DempseyAffiliated withDepartment of Neurosurgery, University of WisconsinDepartment of Neurosurgery and Cardiovascular Research Center, University of Wisconsin Email author 

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Insulin like growth factor-1 (IGF-1) plays an important role in the proliferation and differentiation of neural progenitor cells. The effects of IGF-1 can be regulated by insulin like growth factor binding protein-3 (IGFBP-3) which can either inhibit or stimulate the proliferation of cells depending on the expression of proteases that can release IGF-1 from IGF1-IGFBP3 complex. Although IGF-1 is essential for the development of brain, both IGFBP-3 and IGF-1 are elevated in the brains of children younger than 6 months of age. Likewise, IGFBP-3 is also upregulated following cerebral ischemia and hypoxia. However, the role of IGFBP-3 in neurogenesis is not clear. Using an in vitro culture system of rat neural progenitor cells, we demonstrate that IGFBP-3 specifically regulates the IGF-1 mediated neural progenitor cell proliferation via down regulation of phopho-Akt, and cyclin D1. In addition, IGFBP-3 also decreased the content of nestin in the neural progenitor cells indicating its potential role in neurogenesis.


Neural stem cells Cell cycle Retinoblastoma Neurogenesis