EZH2-dependent myelination following sciatic nerve injury

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外文摘要：Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2fl/fl;Dhh-Cre and Ezh2fl/fl;Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2fl/fl;Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

外文关键词：

demyelinationEZH2myelinationperipheral nerve injuryPRC2remyelinationSchwann cellssciatic nerve crushsciatic nerve transection

作者：

Hui Zhu、Li Mu、Xi Xu、Tianyi Huang、Ying Wang、Siyuan Xu、Yiting Wang、Wencong Wang、Zhiping Wang、Hongkui Wang、Chengbin Xue

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作者单位：

Research Center of Clinical Medicine,Affiliated Hospital of Nantong University,Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education,Co-innovation Center of Neuroregeneration,NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products,Nantong University,Nantong,Jiangsu Province,China

Medical School of Nantong University,Nantong,Jiangsu Province,China

Department of Neurology,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China

Department of Rehabilitation Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China

Department of Critical Care Medicine,Nantong Fourth People,s Hospital,Nantong,Jiangsu Province,China

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-02040

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(8)