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The Expression of IGFBP6 after Spinal Cord Injury: Implications for Neuronal Apoptosis

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Abstract

IGFBP6, a member of the insulin-like growth factor-binding proteins family that contains six high affinity IGFBPs, modulates insulin-like growth factor (IGF) activity and also showed an independent effect of IGF, such as growth inhibition and apoptosis. However, the role of IGFBP6 in spinal cord injury (SCI) remains largely elusive. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of IGFBP6 expression in the spinal cord. Our results showed that IGFBP6 was upregulated significantly after SCI, which was paralleled with the levels of apoptotic proteins p53 and active caspase-3. Immunofluorescent labeling showed that IGFBP6 was co-localizated with active caspase-3 and p53 in neurons. To further investigate the function of IGFBP6, an apoptosis model was established in primary neuronal cells. When IGFBP6 was knocked down by specific short interfering RNA (siRNA), the protein levels of active caspase-3 and Bax as well as the number of apoptotic primary neurons were significantly decreased in our study. Taken together, our findings suggest that the change of IGFBP6 protein expression plays a key role in neuronal apoptosis after SCI.

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Acknowledgements

This work was supported by the following funding, including the Health Research of the Jiangsu Province (Z201316); the Science and Technology of construction and people’s livelihood Foundation of Jiangsu Province (BL2014061); the ‘Top Six Types of Talents’ Financial Assistance of Jiangsu Province Grant (WSW-007).

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    Authors and Affiliations

    1. Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Song Wang, Chunshuai Wu, Jinlong Zhang, Guofeng Bao, Guanhua Xu, Yuyu Sun, Jiajia Chen & Zhiming Cui

    2. Department of Pathogen Biology, Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qi-Xiu Road, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Yonghua Liu

    3. Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Weijuan Zhao

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    1. Song Wang
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    We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

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    Song Wang and Zhiming Cui are contributed equally to this work.

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    Wang, S., Liu, Y., Wu, C. et al. The Expression of IGFBP6 after Spinal Cord Injury: Implications for Neuronal Apoptosis. Neurochem Res 42, 455–467 (2017). https://doi.org/10.1007/s11064-016-2092-9

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