FBXW7alpha Promotes the Recovery of Traumatic Spinal Cord

(E-pub Ahead of Print)

Author(s): Hong Zhang, Tao Yang*.

Journal Name: Current Molecular Medicine

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Abstract:

Background: White matter damage and neuronal cell death is incurred by spinal cord injury (SCI). FBXW7α, an important mediator of cell division and growth was investigated to explore its role in repairing the traumatic spinal cord in rats. Underlying mechanisms such as oxidative stress and inflammasomes signaling were also studied.

Methods: Spinal cord injury in rats was established by longitudinal surgical incision from the lower to mid thoracic vertebrae on the backside, follow by 20-g weight placed on the exposed Th12 surface for 30 min. AAV-delivered FBXW7αand -sh-FBXW7α were intrathecally injected into the rat spinal cord. Indices of oxidation, neurotrophic factors and pyroptosis were measured by Western blot, Elisa and RT-PCR.

Results: We found the overexpression of FBXW7α in spinal cord rescue neuronal death triggered by the injury. Specifically, the nutritional condition, oxidative stress and pyroptosis were improved. A synchronization of BNDF and GDNF expression patterns in various groups indicated the secretion of neurotropic factors affect the outcome of SCI. The SOD1, CAT and GSH-px were suppressed after trauma but all restored in response to FBXW7αoverexpression. Inflammasomes-activated pyroptosis were incurred after the injury, and relevant biomarkers such as GSDMD, caspase-1, caspase-11, IL-1α and IL-18 were down-regulated after the introduction of FBXW7α into the injured cord. Additionally, up-regulating FBXW7αalso repaired the mitochondria dysfunction.

Conclusion: Our data indicate FBXW7αprobably servers as an important molecular target for the therapy of spinal cord injury.

Keywords: FBXW7α, Spinal cord injury, Pyroptosis, Oxidative stress, Caspase signaling, Inflammasomes

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1566524020666191223164916
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