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Critical role of regulator of calcineurin 1 in spinal cord injury

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Abstract

Spinal cord injury (SCI) is a severe clinical problem worldwide. The pathogenesis of SCI is complicated and much is unknown. The current study was designed to investigate the possible role of regulator of calcineurin 1 (RCAN1) in SCI and to explore the possible molecular mechanisms. Rats were injected with LVshRNAi-RCAN1 and then contusion-induced SCI was established. We found that RCAN1 was significantly increased in spinal cord of rats with SCI. Knockdown of RCAN1 markedly facilitated the structural and functional recovery in the spinal cord, as illustrated by decrease of lesion volume and increase of Basso, Beattie, and Bresnahan (BBB) and combined behavioral score (CBS) scores. Downregulation of RCAN1 suppressed the increase of pro-inflammatory cytokines, including IL-1β and TNF-α, and inhibited the increase of TUNEL-positive cell numbers and caspases 3 and 9 activities. The decrease of oxygen consumption rate and increase of expression of glucose-regulated protein 78 (GRP78) and phosphorylation of protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) in rats with SCI were inhibited by LVshRNAi-RCAN1. Moreover, knockdown of RCAN1 ameliorated oxidative stress in rats with SCI, as evidenced by decrease of TBA reactive substances (TBARS) and GSSG content and increase of glutathione (GSH) level. These results suggested that RCAN1 played an important role in SCI through regulation of various pathological processes. Overall, the data provide novel insights into the role of RCAN1 in SCI and novel therapeutic targets of the treatment of injury in the spinal cord.

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Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China

    Guodong Wang, Yilei Zhao, Shenpeng Liu, Jinling Jia & Tan Lu

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  1. Guodong Wang
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  2. Yilei Zhao
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  3. Shenpeng Liu
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  4. Jinling Jia
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  5. Tan Lu
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Correspondence to Guodong Wang.

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All animal experiments were conducted in accordance with the National Institute of Health Guide on the Care and Use of Laboratory Animals and were approved by the Laboratory Animal Users Committee at Xinxiang Medical University (XX201502-3).

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The authors declare that they have no conflicts of interest.

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Wang, G., Zhao, Y., Liu, S. et al. Critical role of regulator of calcineurin 1 in spinal cord injury. J Physiol Biochem 72, 605–613 (2016). https://doi.org/10.1007/s13105-016-0499-z

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  • DOI: https://doi.org/10.1007/s13105-016-0499-z

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