Journal of Cellular Biochemistry

FOXO3a/p27kip1 expression and essential role after acute spinal cord injury in adult rat

Authors

  • Shuangwei Zhang,

    1. Department of Orthopaedics, The Central Hospital of Shijiazhuang, Hebei Province 050011, P.R. China
    2. Jiangsu Key Laboratory of Neuroregeneration, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province 226001, P.R. China
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  • Weipeng Huan,

    1. Jiangsu Key Laboratory of Neuroregeneration, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province 226001, P.R. China
    2. Department of Orthopaedics, The Third People's Hospital of Yancheng, Jiangsu Province 224001, P.R. China
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  • Haixiang Wei,

    1. Jiangsu Key Laboratory of Neuroregeneration, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province 226001, P.R. China
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  • Jinlong Shi,

    1. Jiangsu Key Laboratory of Neuroregeneration, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province 226001, P.R. China
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  • Jinpeng Fan,

    1. Department of Orthopaedics, The Central Hospital of Shijiazhuang, Hebei Province 050011, P.R. China
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  • Jian Zhao,

    1. Jiangsu Key Laboratory of Neuroregeneration, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province 226001, P.R. China
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  • Aiguo Shen,

    1. Jiangsu Key Laboratory of Neuroregeneration, Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province 226001, P.R. China
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  • Prof. Honglin Teng

    Corresponding author
    1. Department of Spine Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China
    • Department of Spine Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
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  • Shuangwei Zhang and Weipeng Huan contributed equally to this work.

Abstract

FOXO3a (Forkhead Class box O3a), as an important direct target of the phosphatidylinositol 3-kinase (PI3K)/protein B (Akt) pathway, which regulates the cell survival and the cell-cycle progression. Recent reports showed that FOXO3a could inhibit cell-cycle progression at the G1/S transition by controlling transcription of the cyclin-dependent kinase inhibitor p27kip1, which is also a key regulator of the mammalian neurogenesis. To elucidate the expression and role of FOXO3a in nervous system lesion and repair, we performed an acute spinal cord contusion injury (SCI) model in adult rats, which showed a temporal–spatial expression pattern of FOXO3a. Temporally, FOXO3a protein level significantly reduced day 3 after injury, and following FOXO3a down-regulation, p27kip1 protein and mRNA levels were also decreased after injury. Spatially, decreased levels of FOXO3a and p27kip1 were predominant in astrocytes, which were regenerating axons and largely proliferated after injury. Furthermore in vitro, Western blot analysis, RT-PCR, and immunofluorescence staining analysis demonstrated the relationship between FOXO3a and p27kip1 in primary astrocytes. FOXO3a modulated the cell cycle by transcriptional regulation of p27kip1 in astrocytes. Administration of the PI3K pharmacological inhibitor LY294002 abrogated this effect by regulating FOXO3a and p27kip1 expression and subcellular localization. These results suggest that decreased levels of FOXO3a and p27kip1 in spinal cord are involved in axonal regeneration and the proliferation of glial cells after SCI. J. Cell. Biochem. 114: 354–365, 2013. © 2012 Wiley Periodicals, Inc.

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