Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury  

作　　者：Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li 

机构地区：[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

出　　处：《Neural Regeneration Research》2025年第6期1749-1763,共15页中国神经再生研究（英文版）

基　　金：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);Graduate Students’ Independent Innovative Projects of Hunan Province,No.CX20230311 (to YJ)。

摘　　要：Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关 键 词：corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury SYRINGIN TRIB2 

分 类 号：R651.2[医药卫生—外科学]