Abstract
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 Statement
Although 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.
Footnotes
The authors declare that they have no conflict of interest.
This work was supported by the Three-year Action Plan (2021-2023) of Shanghai Municipality for Further Accelerating the Inheritance, Innovation and Development of Traditional Chinese Medicine [grant number: ZY(2021-2023)-0205-04].
Availability of data and materials All data in our study are available upon request.
All animal studies were approved by the Animal Experimental Committee of The Sixth People's Hospital [SCXK (Shanghai)2018-0006]
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Jump to comment: