中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (on line): 1-15.

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Enhancing m6A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

  

  • 出版日期:2024-01-01 发布日期:2024-04-01

Tian Qin1, 2, 3, #, Yuxin Jin1, 2, 3, #, Yiming Qin1, 2, 3, Feifei Yuan1, 2, 3, Hongbin Lu2, 3, 4, Jianzhong Hu1, 2, 3, *, Yong Cao1, 2, 3, *, Chengjun Li2, 3, 4, *   

  1. 1 Department of Spine Surgery and Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 2 Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan Province, China; 3 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 4 Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Online:2024-01-01 Published:2024-04-01
  • Contact: Jianzhong Hu, PhD, jianzhonghu@csu.edu.cn, or jianzhonghu@hotmail.com; Yong Cao, PhD, xycaoyong@csu.edu.cn, or caoyong1912@163.com; Chengjun Li, PhD, 443555063@qq.com, or lichengjun1992@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82030071 (to JH), 82272495 (to YC); Science and Technology Major Project of Changsha, No. kh2103008 (to JH); and Graduate Students’ Independent Innovative Projects of Hunan Province, No. CX20230311 (to YJ).

摘要: https://orcid.org/0009-0006-7192-5774 (Jianzhong Hu); https://orcid.org/0000-0002-9618-4734 (Yong Cao); https://orcid.org/0000-0002-4307-5235 (Chengjun Li)

Abstract: Spinal cord injury (SCI) typically causes corticospinal tract (CST) disruption. Although the disrupted CST can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine (m6A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m6A modifications participate in CST regeneration after SCI remains unknown. We found that expression of methyltransferase 14 protein (METTL14) in the locomotor cortex was high after SCI and accompanied by elevated m6A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for CST regeneration and neurological recovery after SCI. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m6A-regulated manner, thereby activating the mitogenactivated protein kinase pathway and promoting CST regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote CST regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m6 A modification is involved in the regulation of CST regeneration after spinal cord injury.

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