Electroacupuncture (EA) is widely applied in clinical therapy for spinal cord injury (SCI). However, the associated molecular mechanism has yet to be elucidated. The current study aimed to investigate the underlying mechanism of electroacupuncture in neurological repair after spinal cord injury.
Firstly, we investigated the role of electroacupuncture in the neurological repair of the spinal cord injury rat model. The expression levels of Human antigen R (HuR) and Kruppel-like factor 9 (KLF9) in spinal cord tissues were quantified after electroacupuncture treatment. Secondly, we carried out bioinformatics analysis, RNA pull-down assay, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Lastly, HuR inhibitor CMLD-2 was used to verify the enhanced effect of electroacupuncture on neurological repair after spinal cord injury via the HuR/KLF9 axis.
Our data provided convincing evidence that electroacupuncture facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that electroacupuncture significantly diminished the SCI-mediated upregulation of HuR, and HuR could bind to the 3’UTR region of KLF9 mRNA to protect its decay. In addition, a series of in vivo experiments confirmed that CMLD-2 administration increased electroacupuncture-mediated pain thresholds and motor function in spinal cord injury rats.
Collectively, the present study showed that electroacupuncture improved pain thresholds and motor function in spinal cord injury rats via impairment of HuR-mediated KLF9 mRNA stabilisation, thus, providing a better understanding of the regulatory mechanisms regarding electroacupuncture-mediated neurological repair after spinal cord injury.
Significance Statement: Although electroacupuncture has been used to treat spinal cord injury in recent years, its regulatory mechanism has not yet been clarified. To elucidate the molecular mechanism of electroacupuncture in reducing spinal cord injury, we conducted a series of in vivo and in vitro experiments. Electroacupuncture contributes to neurological repair of spinal cord injury rats through diminishing the SCI-mediated upregulation of HuR and KLF9. Additionally, electroacupuncture‘s downstream target HuR physically interacted with the 3’UTR region of KLF9 mRNA to protect its decay. These findings provide a connection between electroacupuncture and neuron repair. Furthermore, this study also provides theoretical basis for electroacupuncture in the clinical treatment of spinal cord injury.