Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (8): 2382-2394.doi: 10.4103/NRR.NRR-D-23-02040

Previous Articles     Next Articles

EZH2-dependent myelination following sciatic nerve injury

Hui Zhu1, #, Li Mu2, 3, #, Xi Xu1, 4, #, Tianyi Huang2 , Ying Wang2, 3, Siyuan Xu2, 3, Yiting Wang2, 3, Wencong Wang2, 3, Zhiping Wang2, 5, *, Hongkui Wang1, *, Chengbin Xue1, *   

  1. 1 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Coinnovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu Province, China;  2 Medical School of Nantong University, Nantong, Jiangsu Province, China;  3 Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China;  4 Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China;  5 Department of Critical Care Medicine, Nantong Fourth People’s Hospital, Nantong, Jiangsu Province, China
  • Online:2025-08-15 Published:2024-12-14
  • Contact: Chengbin Xue, PhD, xuechengbin@ntu.edu.cn; Hongkui Wang, PhD, wanghongkui@ntu.edu.cn; Zhiping Wang, MD, 18888058897@139.com.
  • Supported by:
    This work was financially supported by the National Natural Science Foundation of China, Nos. 82172104 (to CX), 81873767 (to HZ); a grant from Jiangsu Provincial Research Hospital, Nos. YJXYY202204 (to HZ), YJXYY202204-ZD04 (to HZ); a grant from Jiangsu Provincial Key Medical Center, Jiangsu Provincial Medical Innovation Center, No. CXZX202212; Jiangsu Provincial Medical Key Discipline, No. ZDXK202240; the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Technology Project of Nantong, No. MS22022008 (to HZ); and Postgraduate Research & Practice Innovation Program of Jiangsu Province, No. SJCX21_1457 (to WW).

PDF

18

Abstract: 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.

Key words: demyelination,  EZH2,  myelination,  peripheral nerve injury,  PRC2,  remyelination,  Schwann cells,  sciatic nerve crush,  sciatic nerve transection