Abstract：
Recent studies have shown that autophagy is activated in response to nerve damage and occurs simultaneously with the initial stages of Schwann cell-mediated demyelination. Although several studies have reported that macroautophagy is involved in the peripheral nerve, the role of chaperone-mediated autophagy (CMA) has not yet been investigated in peripheral nerve injury. The present study investigates the role of CMA in the sciatic nerve. Using a mouse model of sciatic nerve injury, the authors employed immunofluorescence analysis to observe the expression of LAMP2A, a critical marker for CMA. RNA sequencing was performed to observe the transcriptional profile of Lamp2a in Schwann cells. Bioinformatics analysis was carried out to observe the hub genes associated with Lamp2a . Expression of Lamp2a , a key gene in CMA, increased following sciatic nerve injury, based on an immunofluorescence assay. To identify differentially expressed genes using Lamp2a , RNA sequence analysis was conducted using rat Schwann cells overexpressing Lamp2a . The nine hub genes ( Snrpf, Polr1d, Snip1, Aqr, Polr2h, Ssbp1, Mterf3, Adcy6 , and Sbds ) were identified using the CytoHubba plugin of Cytoscape. Functional analysis revealed that Lamp2a overexpression affected the transcription levels of genes associated with mitotic spindle organization and mRNA splicing via the spliceosome. In addition, Polr1d and Snrpf1 were downregulated throughout postnatal development but elevated following sciatic nerve injury, according to a bioinformatics study. CMA may be an integral pathway in sciatic nerve injury via mRNA splicing.
摘要：
最近的研究表明，自噬是响应神经损伤而激活的，并且与雪旺氏细胞介导的脱髓鞘的初始阶段同时发生。尽管有一些研究报道巨自噬与周围神经有关，伴侣介导的自噬(CMA)在周围神经损伤中的作用尚未被研究.本研究调查了CMA在坐骨神经中的作用。使用坐骨神经损伤的小鼠模型，作者采用免疫荧光分析观察LAMP2A的表达，CMA的关键标记。进行RNA测序以观察Lamp2a在雪旺氏细胞中的转录谱。进行生物信息学分析以观察与Lamp2a相关的hub基因。Lamp2a的表达，CMA的关键基因,坐骨神经损伤后增加，基于免疫荧光分析。为了使用Lamp2a鉴定差异表达的基因，使用过表达Lamp2a的大鼠雪旺氏细胞进行RNA序列分析。九个中心基因(Snrpf，Polr1d,Snip1,Aqr,Polr2h,Ssbp1，Mterf3，Adcy6和Sbds）是使用Cytoscape的CytoHubba插件鉴定的。功能分析显示，Lamp2a过表达通过剪接体影响有丝分裂纺锤体组织和mRNA剪接相关基因的转录水平。此外,Polr1d和Snrpf1在整个出生后发育过程中下调，但在坐骨神经损伤后升高，根据一项生物信息学研究。CMA可能是通过mRNA剪接的坐骨神经损伤的整合途径。
