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Upregulation of Interferon Regulatory Factor 6 Promotes Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats

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Abstract

The interferon regulatory factor (IRF) family was first discovered as a set of transcriptional regulators of the type I interferon system in 1988. In mammals, the IRF family includes nine members that play important roles in the immune system, oncogenesis, and apoptosis. However, the distribution and the function of IRF6 in the central nervous system are limited. In this study, we established an adult rat traumatic brain injury (TBI) model. Compared to the sham brain cortex, Western blot and immunohistochemistry showed significant upregulation of IRF6 in the ipsilateral brain cortex after TBI. Immunofluorescence double-labeling showed that IRF6 completely co-localized with neurons, not astrocytes or oligodendrocytes. Furthermore, we detected that the neuronal apoptosis marker active caspase-3 co-localized with IRF6 in neurons. Additionally, IRF6 knockdown in PC12 cells in vitro resulted in a decrease in active caspase-3 expression and an increase in Bcl-2 and p-Akt expression. We conclude that IRF6 might promote neuronal apoptosis by inhibiting Akt phosphorylation after TBI.

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Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (Nos. 81401365, 81373223, 81200918, 81172879 and 31200800) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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    Authors and Affiliations

    1. Department of Neurosurgery, Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, 214002, Jiangsu, People’s Republic of China

      Yuchang Lin & Dezhi Xu

    2. Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Xiaohong Li

    3. Laboratory Animal Center, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Chun Liu

    4. Department of Pathophysiology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Xia Liu

    5. Department of Osteology, Second Affiliated Hospital, Nantong University, Nantong, 226001, People’s Republic of China

      Shen Huang

    6. Institute of Navigation Medicine, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Yuwei Huang

    7. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Xiaojuan Liu

    8. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Yuchang Lin, Dezhi Xu, Xiaohong Li, Chun Liu, Xia Liu, Shen Huang, Yuwei Huang & Xiaojuan Liu

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    1. Yuchang Lin
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    Correspondence to Xiaojuan Liu.

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    Yuchang Lin and Dezhi Xu contributed equally to this work.

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    Lin, Y., Xu, D., Li, X. et al. Upregulation of Interferon Regulatory Factor 6 Promotes Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats. Cell Mol Neurobiol 36, 27–36 (2016). https://doi.org/10.1007/s10571-015-0217-3

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