Downregulated CAV-1 in mouse spinal cord may alleviate bone cancer pain by inhibiting the ERK/CREB pathway

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2023-07-01 DOI:10.1016/j.mrfmmm.2023.111829

Jianyun Ge , Jie Song , Bo Sun , Xuefeng Yang , Boxiang Du , Xin Sun , Jiejie Zhang , Jianlin Ge , Hong Xie

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Abstract

Background

This study aimed to assess the potential function of Caveolin-1 (CAV-1) in mice with bone cancer pain. Method: Using a mice bone cancer pain model we explored the contribution of CAV-1 expression to bone cancer pain on the 14th day after surgery, mice in the tumor group were randomized and treated with increasing doses of the CAV-1 inhibitor, methyl-beta-cyclodextrin. Pain was assessed by monitoring the number of spontaneous flinches (NSF) and paw withdrawal mechanical threshold (PMWT)mechanical withdrawal threshold (MWT). The localization and expression of CAV-1 in mouse neurons was also determined. Additionally, the protein levels of CAV-1, extracellular signal regulated kinase (ERK) 1/2, cAMP response element-binding protein (CREB) were monitored in mouse spinal cord tissues by western blotting. Results: CAV-1 was remarkably upregulated in the spinal cord of the tumor group on the 4th day after surgery, then downregulated on day 10, and upregulated again at day 14. Such CAV-1 levels were maintained until day 28. In the tumor group, the expression of p-ERK1/2 and p-CERB were upregulated at day 14 after surgery. Intrathecal injection of methyl-beta-cyclodextrin (MCD) downregulated p-ERK1/2 and p-CERB expression which correlated with alleviation of pain. Conclusion: Inhibition of CAV-1 in the spinal cord alleviates bone cancer pain in mice which correlates with inhibition of the ERK/CREB pathway.

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小鼠脊髓CAV-1下调可能通过抑制ERK/CREB途径减轻骨癌症疼痛

背景本研究旨在评估Caveolin-1（CAV-1）在骨癌症疼痛小鼠中的潜在功能。方法：采用小鼠骨癌症疼痛模型，探讨手术后第14天CAV-1表达对骨癌症疼痛的贡献。肿瘤组小鼠随机分为两组，分别用增加剂量的CAV-1抑制剂甲基-β-环糊精治疗。通过监测自发退缩次数（NSF）和爪退缩机械阈值（PMWT）机械阈值（MWT）来评估疼痛。还测定了CAV-1在小鼠神经元中的定位和表达。此外，通过蛋白质印迹法监测小鼠脊髓组织中CAV-1、细胞外信号调节激酶（ERK）1/2、cAMP反应元件结合蛋白（CREB）的蛋白水平。结果：CAV-1在术后第4天在肿瘤组脊髓中显著上调，第10天下调，第14天再次上调。这种CAV-1水平一直维持到第28天。在肿瘤组中，p-ERK1/2和p-CERB的表达在手术后第14天上调。鞘内注射甲基β-环糊精（MCD）下调p-ERK1/2和p-CERB的表达，这与减轻疼痛有关。结论：抑制脊髓CAV-1可减轻小鼠癌症骨痛，这与抑制ERK/CREB通路有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.