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Peripheral Nerve Injury Induces Down-Regulation of Foxo3a and p27kip1 in Rat Dorsal Root Ganglia

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Abstract

FOXO3a, as a forkhead transcription factor, can control cell cycle through transcriptionally down-regulating p27kip1 level, which is a key regulator of the mammalian cell cycle and a good candidate to regulate multiple aspects of neurogenesis. To elucidate their expression and function in nervous system lesion and repair, we performed an acute sciatic nerve crush model and studied differential expressions of Foxo3a and p27kip1 in lumbar dorsal root ganglia. Temporally, Foxo3a protein level was reduced 1 day after injury, and following Foxo3a down-regulation, p27kip1 mRNA and protein levels were also decreased after injury. Spatially, decreased levels of Foxo3a and p27kip1 were predominant in neurons and glial cells, which were regenerating axons and largely proliferated after injury, respectively. Together with previous reports, we hypothesized decreased levels of Foxo3a and p27kip1 in lumbar dorsal root ganglia were implicated in axonal regeneration and the proliferation of glial cells after sciatic nerve injury.

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Abbreviations

CNS:

Central nervous system

DRG:

Dorsal root ganglia

FOXO:

Forkhead box class O

CDK2:

Cyclin-dependent kinase 2

PI3-K:

Phosphatidylinositol 3-kinase

SGK:

Serum and glucocorticoid–induced kinase

PAGE:

Polyacrylamide gel electrophoresis

ECL:

Enhanced chemiluminescence system

BSA:

Bovine serum albumin

NeuN:

Neuronal nuclei

PCNA:

Proliferating cell nuclear antigen

GFAP:

Glial fibrillary acidic protein

GAP-43:

Neuronal growth-associated protein-43

RT-PCR:

Reverse transcriptase PCR

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgments

This work was supported by the National Natural Scientific Foundation of China Grant (No. 30300099 and No. 30770488), Natural Scientific Foundation of Jiangsu Province Grant (No. BK2003035 and No. BK2006547), College and University Natural Scientific Research Programme of Jiangsu Province (No. 03KJB180109 and No. 04KJB320114), Technology Guidance Plan for Social Development of Jiangsu Province Grant (BS2004526), Health Project of Jiangsu Province (H200632), “Liu-Da-Ren-Cai-Gao-Feng” Financial Assistance of Jiangsu Province Grant (No. 2), Postgraduate Scientic Innovation Program of Jiangsu Province (No. CX08S_026Z).

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Authors and Affiliations

  1. Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, China

    Youhua Wang

  2. The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, 19 Qi-xiu Road, Nantong, 226001, China

    Youhua Wang, Yonghua Liu & Aiguo Shen

  3. Department of Microbiology and Immunology, Medical College, Nantong University, Nantong, 226001, China

    Youhua Wang, Yonghua Liu, Shuxian Shi, Feng Xiao, Dan Zhou, Mudan Lu, Qiuyan Lu & Aiguo Shen

  4. Department of Histology and Embryology, Medical College, Nantong University, Nantong, 226001, China

    Ying Chen

  5. Department of Pathology, Medical College, Nantong University, Nantong, 226001, China

    Jing Qin

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  1. Youhua Wang
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  2. Yonghua Liu
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Correspondence to Aiguo Shen.

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Youhua Wang and Yonghua Liu have contributed equally to this work.

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Wang, Y., Liu, Y., Chen, Y. et al. Peripheral Nerve Injury Induces Down-Regulation of Foxo3a and p27kip1 in Rat Dorsal Root Ganglia. Neurochem Res 34, 891–898 (2009). https://doi.org/10.1007/s11064-008-9849-8

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  • DOI: https://doi.org/10.1007/s11064-008-9849-8

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