LncRNA ZFAS1联合SRSF1调控CNPY2表达导致小胶质细胞内质网应激性脊髓损伤

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-04 DOI:10.1007/s12035-025-05080-4
Pengcheng Chen, Zhong Huang, Yiheng Liu
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引用次数: 0

摘要

脊髓损伤(SCI)具有很高的死亡率和致残率。内质网应激诱导神经元凋亡,参与脊髓损伤的调节。LncRNA ZFAS1可通过影响内质网应激参与SCI的调控;但其作用机制值得进一步探讨。通过体外和体内实验,探讨lncRNA ZFAS1调控脊髓损伤的分子机制。我们用LPS诱导小鼠小胶质细胞(BV-2),建立体外脊髓损伤模型。通过转染shRNA敲低lncRNA、ZFAS1和CNPY2,证实了SCI的调控作用。采用qPCR和western blot检测相关基因和蛋白的表达水平。流式细胞术、TUNEL染色分析细胞凋亡比例。RIP和RNA pull down验证lncRNA ZFAS1与SRSF1联合稳定了CNPY2 mRNA。在脊髓损伤小鼠模型中证实lncRNA ZFAS1促进内质网应激,加速脊髓损伤。我们的研究结果显示,lncRNA ZFAS1和CNPY2在脊髓损伤细胞模型中表达增加,与脊髓损伤有关。敲低lncRNA ZFAS1或CNPY2可抑制内质网应激,减少BV-2细胞凋亡。抑制lncRNA ZFAS1可增加脊髓损伤小鼠脊髓神经元数量和内质网应激反应,改善脊髓损伤。分子实验证实lncRNA ZFAS1通过结合SRSF1稳定CNPY2 mRNA。lncRNA ZFAS1/CNPY2轴参与调控内质网应激和BV-2细胞凋亡。LncRNA ZFAS1通过与SRSF1联合稳定CNPY2,导致小胶质细胞内质网应激,促进脊髓损伤。LncRNA ZFAS1可能是预防和治疗脊髓损伤的潜在靶基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
LncRNA ZFAS1 Combined with SRSF1 Regulate CNPY2 Expression and Leads to Microglia Endoplasmic Reticulum Stress-Induced Spinal Cord Injury.

Spinal cord injury (SCI) has a high mortality and disability rate. Endoplasmic reticulum (ER) stress induces neuronal apoptosis and participates in the regulation of SCI. LncRNA ZFAS1 can participate in the regulation of SCI by influencing ER stress; however, its mechanism is worth further exploring. The molecular mechanism of lncRNA ZFAS1 regulating spinal cord injury was evaluated by in vitro and in vivo experiments. We established an SCI model in vitro by inducing mouse microglia (BV-2) with LPS. The regulation of SCI was verified by transfection of shRNA knockdown lncRNA ZFAS1 and CNPY2. The expression levels of related genes and proteins were detected by qPCR and western blot. The proportion of apoptosis was analyzed by flow cytometry and TUNEL staining. RIP and RNA pull down verified that lncRNA ZFAS1 combined with SRSF1 stabilized CNPY2 mRNA. It was verified that lncRNA ZFAS1 promoted ER stress and accelerated SCI injury in SCI mice model. Our results showed that the expression of lncRNA ZFAS1 and CNPY2 increased in SCI cell model, which was related to SCI injury. Knocking down lncRNA ZFAS1 or CNPY2 could inhibit ER stress and reduce apoptosis of BV-2 cells. Inhibition of lncRNA ZFAS1 in SCI mice increased the number of spinal cord neurons and ER stress response, and improved SCI injury in mice. Molecular experiments confirmed that lncRNA ZFAS1 stabilized CNPY2 mRNA by binding to SRSF1. And the lncRNA ZFAS1/CNPY2 axis was involved in regulating ER stress and apoptosis of BV-2 cells. LncRNA ZFAS1 stabilized CNPY2 by combining with SRSF1, which led to ER stress in microglia and promoted SCI. LncRNA ZFAS1 may be a potential target gene for the prevention and treatment of SCI.

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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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