Title:FBXW7alpha Promotes the Recovery of Traumatic Spinal Cord
Volume: 20
Issue: 6
Author(s): Hong Zhang and Tao Yang*
Affiliation:
- Department of Orthopedics, 4th (Xing Yuan) Hospital of Yulin, Yulin City, Shaanxi Province, 719000,China
Keywords:
FBXW7α, spinal cord injury, pyroptosis, oxidative stress, caspase signaling, inflammasomes.
Abstract:
Background: White matter damage and neuronal cell death are 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, followed by 20-g weight placed on
the exposed Th12 surface for 30 min. AAV-delivered FBXW7α and -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 neurotrophic factors affect the outcome of SCI.
The SOD1, CAT, and GSH-px were suppressed after trauma but all restored in
response to FBXW7α overexpression. Inflammasomes-activated pyroptosis was
incurred after the injury, and relevant biomarkers such as GSDMD, caspase-1, caspase-
11, IL-1β, and IL-18 were down-regulated after the introduction of FBXW7α into the
injured cord. Additionally, up-regulating FBXW7α also repaired the mitochondria
dysfunction.
Conclusion: Our data indicate FBXW7α probably serves as an important molecular
target for the therapy of spinal cord injury.