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

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外文摘要：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(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 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 m6A 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 m6A-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 m6A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

外文关键词：

corticospinal tract remodelingepigenetic regulationslocomotor cortexm6A modificationmethyltransferase 14 protein(METTL14)mitogen-activated protein kinaseneural regenerationspinal cord injurysyringinTRIB2

作者：

Tian Qin、Yuxin Jin、Yiming Qin、Feifei Yuan、Hongbin Lu、Jianzhong Hu、Yong Cao、Chengjun Li

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作者单位：

Department of Spine Surgery and Orthopedics,Xiangya Hospital,Central South University,Changsha,Hunan Province,China

Key Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,Hunan Province,China

National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha,Hunan Province,China

Department of Sports Medicine,Xiangya Hospital,Central South University,Changsha,Hunan Province,China

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01477

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(6)