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International Journal of Molecular Medicine
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Article

The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression

  • Authors:
    • Honghui Lu
    • Li-Hai Zhang
    • Lin Yang
    • Pei-Fu Tang
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100853, P.R. China, Department of Orthopaedics, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Orthopaedics, The Third Hospital of Beijing Municipal Corps, Chinese People's Armed Police Forces, Beijing 100141, P.R. China
  • Pages: 2832-2838
    |
    Published online on: February 6, 2018
       https://doi.org/10.3892/ijmm.2018.3459
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Abstract

The aim of the present study was to elucidate the expression and role of the phosphatidylinositol 3‑kinase (PI3K)/Akt/forkhead box O3 (FOXO3a) pathway in the regeneration of the spinal cord following spinal cord injury (SCI), and its regulatory effect on tumor necrosis factor (TNF)-α and cyclin-dependent kinase inhibitor 1B (p27kip1) expression. Firstly, in a Sprague-Dawley rat model of SCI, western blot analysis revealed that the protein levels of PI3K, phosphorylated Akt and FOXO3a were markedly inhibited compared with those in the sham control group. In vitro experiments were also conducted, in which primary dissociated cultures of rat dorsal spinal cord cells were induced with lipopolysaccharide (LPS; 4 µg/ml). The downregulation of PI3K using LY294002 markedly suppressed cell viability, reduced the protein levels of FOXO3a and p27kip1, and increased TNF-α protein production in the LPS-induced spinal cord cells. In addition, when the LPS-induced spinal cord cells were infected with FOXO3a adenoviral vectors, the overexpression of FOXO3 markedly promoted cell proliferation, activated p27kip1 protein levels and inhibited TNF-α protein production in the spinal cord cells. These results suggest that the PI3K/Akt/FOXO3a pathway regulates regeneration following SCI in adult rats via its modulatory effects on TNF-α and p27kip1 expression.
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Copy and paste a formatted citation
Spandidos Publications style
Lu H, Zhang L, Yang L and Tang P: The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression. Int J Mol Med 41: 2832-2838, 2018.
APA
Lu, H., Zhang, L., Yang, L., & Tang, P. (2018). The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression. International Journal of Molecular Medicine, 41, 2832-2838. https://doi.org/10.3892/ijmm.2018.3459
MLA
Lu, H., Zhang, L., Yang, L., Tang, P."The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression". International Journal of Molecular Medicine 41.5 (2018): 2832-2838.
Chicago
Lu, H., Zhang, L., Yang, L., Tang, P."The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression". International Journal of Molecular Medicine 41, no. 5 (2018): 2832-2838. https://doi.org/10.3892/ijmm.2018.3459
Copy and paste a formatted citation
x
Spandidos Publications style
Lu H, Zhang L, Yang L and Tang P: The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression. Int J Mol Med 41: 2832-2838, 2018.
APA
Lu, H., Zhang, L., Yang, L., & Tang, P. (2018). The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression. International Journal of Molecular Medicine, 41, 2832-2838. https://doi.org/10.3892/ijmm.2018.3459
MLA
Lu, H., Zhang, L., Yang, L., Tang, P."The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression". International Journal of Molecular Medicine 41.5 (2018): 2832-2838.
Chicago
Lu, H., Zhang, L., Yang, L., Tang, P."The PI3K/Akt/FOXO3a pathway regulates regeneration following spinal cord injury in adult rats through TNF-α and p27kip1 expression". International Journal of Molecular Medicine 41, no. 5 (2018): 2832-2838. https://doi.org/10.3892/ijmm.2018.3459
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