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Silencing the enhancer of zeste homologue 2,Ezh2,represses axon regeneration of dorsal root ganglion neurons

Neural Regeneration Research 2022年第7期17卷 1518-1525页

作者： Ting-Ting Guo Ying Zhao Wei-Xiao Huang Tao Zhang Li-Li Zhao Xiao-Song Gu Song-Lin Zhou Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsJiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury RepairCo-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease Nanjing UniversityNanjingJiangsu ProvinceChina

Recovery from injury to the peripheral nervous system is different from that of the central nervous system in that it can lead to gene reprogramming that can induce the expression of a series of regeneration-associated *** eventually leads to axonal regeneration of injured *** some regeneration-related genes have been identified,the regulatory network underlying axon regeneration remains largely *** explore the regulator of axon regeneration,we performed RNA sequencing of lumbar L4 and L5 dorsal root ganglion(DRG)neurons at different time points(0,3,6,12 hours,1,3 and 7 days)after rat sciatic nerve *** isolation of neurons was carried out by laser capture microscopy combined with NeuN immunofluorescence *** found 1228 differentially expressed genes in the injured sciatic nerve *** hub genes within these differentially expressed genes include Atf3,Jun,Myc,Ngf,Fgf2,Ezh2,Gfap and *** verified that the expression of the enhancer of zeste homologue 2 gene(Ezh2)was up-regulated in DRG neurons after injury,and this up-regulation differed between large-and small-sized dorsal root ganglion *** investigate whether the up-regulation of Ezh2 impacts axonal regeneration,we silenced Ezh2 with siRNA in cultured DRG neurons and found that the growth of the newborn axons was *** our investigation into the regulatory network of Ezh2 by interpretive phenomenal analysis,we found some regulators of Ezh2(including Erk,Il6 and Hif1a)and targets(including Atf3,Cdkn1a and Smad1).Our findings suggest that Ezh2,as a nerve regeneration-related gene,participates in the repair of the injured DRG neurons,and knocking down the Ezh2 in vitro inhibits the axonal growth of DRG *** the experimental procedures approved by the Administration Committee of Experimental Animals of Jiangsu Province of China(approval No.S20191201-201)on March 21,2019.

关键词： axon regeneration dorsal root ganglion neurons Ezh2 IB4 laser capture microscopy nf160/200 quantitative reverse transcription-polymerase chain reaction sciatic nerve crush scRNA-seq siRNA

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