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AKR1B1 Upregulation Contributes to Neuroinflammation and Astrocytes Proliferation by Regulating the Energy Metabolism in Rat Spinal Cord Injury

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Abstract

Spinal cord injury (SCI) is one of the most common and serious condition, which leads to permanent neurological dysfunction and poor prognosis in patients. Hyperglycemia impairs neural functional recovery after SCI resulting in the overproduction of reactive oxygen species (ROS) and inflammatory cytokines. However, the effect of glucose metabolism in the spinal cord after injury remains unclear. AKR1B1, one member of the aldo/keto reductase superfamily, is involved in the energy metabolism of plasm glucose and ROS production. The role of AKR1B1 in cancer cell proliferation and invasion has been confirmed. Meanwhile, Akt, one pivotal transcription factor particularly, is involved in the regulation of cell cycle and ROS-mediated secondary injury in the lesion site. In our study, we established an acute SCI rat model to identify the expression of AKR1B1 and its role in neural recovery processes. Western blotting revealed the expression of AKR1B1 protein was elevated after injury, peaked at 3 days and declined gradually to normal at 14 days. Similar results was illustrated in immunohistochemistry staining of white matter. Double immunofluorescence staining showed AKR1B1 was expressed in glial cells and its expression was significantly increased in proliferative astrocytes during the pathological processes. Further experiments showed AKR1B1 was co-located with Akt protein in GFAP positive cells and immunoprecipitated with Akt in injured spinal cord as well. In summary, the present study demonstrated AKR1B1 played a vital role in astrocytes proliferation through Akt pathway, associated with the metabolism of hyperglycemia induced by SCI.

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Abbreviations

SCI:

Spinal cord injury

AKR1B1:

Aldo–keto reductase family 1 member B1

GFAP:

Glial fibrillary acidic protein

PCNA:

Proliferating cell nuclear antigen

siRNA:

Short interfering RNA

CNS:

Central nervous system

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Author notes

  1. Xiaoqing Chen and Cheng Chen have equally contributed to this work.

Authors and Affiliations

  1. Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Xiaoqing Chen, Cheng Chen, Jie Hao, Rongqing Qin, Baiyu Qian, Kai Yang & Feng Zhang

  2. Department of Radiology, Third Municipal People’s Hospital, Nantong, 226001, Jiangsu, China

    Jiyun Zhang

  3. Medical Colleges of Nantong University, Nantong, 226001, Jiangsu, China

    Cheng Chen, Rongqing Qin, Baiyu Qian, Kai Yang & Jiyun Zhang

  4. Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong, 226001, Jiangsu, China

    Xiaoqing Chen, Jie Hao & Feng Zhang

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  1. Xiaoqing Chen
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  2. Cheng Chen
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Correspondence to Feng Zhang.

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Chen, X., Chen, C., Hao, J. et al. AKR1B1 Upregulation Contributes to Neuroinflammation and Astrocytes Proliferation by Regulating the Energy Metabolism in Rat Spinal Cord Injury. Neurochem Res 43, 1491–1499 (2018). https://doi.org/10.1007/s11064-018-2570-3

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  • DOI: https://doi.org/10.1007/s11064-018-2570-3

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