RT Journal Article
SR Electronic
T1 Electroacupuncture relieves HuR/KLF9-mediated inflammation to enhance neurological repair after spinal cord injury
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0190-23.2023
DO 10.1523/ENEURO.0190-23.2023
A1 Zhang, Junfeng
A1 Xu, JingJie
A1 Li, ShiSheng
A1 Chen, Wei
A1 Wu, YaoChi
YR 2023
UL http://www.eneuro.org/content/early/2023/11/07/ENEURO.0190-23.2023.abstract
AB Electro-acupuncture (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 EA in neurological repair after SCI. Firstly, we investigated the role of EA in the neurological repair of the SCI rat model. The expression levels of Human antigen R (HuR) and Kruppel-like factor 9 (KLF9) in spinal cord tissues were quantified after EA 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 EA on neurological repair after SCI via the HuR/KLF9 axis. Our data provided convincing evidence that EA facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that EA 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 EA-mediated pain thresholds and motor function in SCI rats. Collectively, the present study showed that EA improved pain thresholds and motor function in SCI rats via impairment of HuR-mediated KLF9 mRNA stabilization, thus, providing a better understanding of the regulatory mechanisms regarding EA-mediated neurological repair after SCI.Significance StatementAlthough EA has been used to treat SCI in recent years, its regulatory mechanism has not yet been clarified. To elucidate the molecular mechanism of EA in reducing SCI, we conducted a series of in vivo and in vitro experiments.EA contributes to neurological repair of SCI rats through diminishing the SCI-mediated upregulation of HuR and KLF9. Additionally, EA's downstream target HuR physically interacted with the 3’UTR region of KLF9 mRNA to protect its decay. These findings provide a connection between EA and neuron repair. Furthermore, this study also provides theoretical basis for EA in the clinical treatment of SCI.