Transcriptional genes of lysosome-associated membrane protein 2A in sciatic nerve injuries by bioinformatics.

IF 1.6 4区 医学 Q4 NEUROSCIENCES Neuroreport Pub Date : 2024-08-07 Epub Date: 2024-06-19 DOI:10.1097/WNR.0000000000002066
Eun Jung Sohn, Kun-Taek Park
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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.

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通过生物信息学分析坐骨神经损伤中溶酶体相关膜蛋白 2A 的转录基因
最近的研究表明,自噬在神经损伤时被激活,并与许旺细胞介导的脱髓鞘初期阶段同时发生。虽然一些研究报告称大自噬参与了周围神经的损伤,但尚未研究伴侣介导的自噬(CMA)在周围神经损伤中的作用。本研究探讨了 CMA 在坐骨神经中的作用。作者利用坐骨神经损伤小鼠模型,采用免疫荧光分析法观察 CMA 的关键标记物 LAMP2A 的表达。他们还进行了 RNA 测序,以观察 Lamp2a 在许旺细胞中的转录情况。进行生物信息学分析以观察与 Lamp2a 相关的枢纽基因。根据免疫荧光检测,坐骨神经损伤后,CMA 的关键基因 Lamp2a 的表达增加。为了确定与 Lamp2a 有差异表达的基因,使用过表达 Lamp2a 的大鼠许旺细胞进行了 RNA 序列分析。利用 Cytoscape 的 CytoHubba 插件确定了九个中心基因(Snrpf、Polr1d、Snip1、Aqr、Polr2h、Ssbp1、Mterf3、Adcy6 和 Sbds)。功能分析显示,Lamp2a 的过表达影响了与有丝分裂纺锤体组织有关的基因的转录水平,并通过剪接体影响了 mRNA 的剪接。此外,根据一项生物信息学研究,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。CMA可能是通过mRNA剪接造成坐骨神经损伤的一个不可或缺的途径。
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来源期刊
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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