IGFBP-3 Inhibits the Proliferation of Neural Progenitor Cells
IGFBP-3 Inhibits the Proliferation of Neural Progenitor Cells
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DOI：
10.1007/s11064-010-0349-2
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发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Dempsey, Robert J.
中科院分区：
文献类型：
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作者：
Kalluri, Haviryaji S. G.;Dempsey, Robert J.
胰岛素样生长因子-1(IGF-1)在神经前体细胞的增殖和分化中起重要作用。IGF-1的作用受胰岛素样生长因子结合蛋白-3(IGFBP-3)的调节，IGFBP-3可以抑制或刺激细胞的增殖，这取决于从IGF1-IGFBP3复合体中释放IGF-1的蛋白的表达。虽然IGF-1对大脑发育是必不可少的，但IGFBP-3和IGF-1在6个月以下的儿童大脑中都升高。同样，IGFBP-3在脑缺血和缺氧后也会上调。然而，IGFBP-3在神经发生中的作用尚不清楚。利用大鼠神经前体细胞体外培养系统，我们证明了IGFBP-3通过下调磷酸化Akt和细胞周期蛋白D1来特异性地调节IGF-1介导的神经前体细胞的增殖。此外，IGFBP-3还可降低神经前体细胞中巢蛋白的含量，提示其在神经发生中的潜在作用。
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.