Abstract
Human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), remains one of the most diverse crucial health and development challenges around the world. People infected with HIV constitute a large patient population, and a significant number of them experience neuropathic pain. To study the key mechanisms that mediate HIV-induced neuropathic pain (HNP), we established an HNP mouse model via intrathecal injection of the HIV-1 envelope glycoprotein gp120. The L3~L5 spinal cord was isolated on postoperative days 1/12 (POD1/12), 1 (POD1), and 14 (POD14) for RNA sequencing to investigate the gene expression profiles of the initiation, transition, and maintenance stages of HNP. A total of 1682, 430, and 413 differentially expressed genes were obtained in POD1/12, POD1, and POD14, respectively, and their similarity was low. Bioinformatics analysis confirmed that POD1/12, POD1, and POD14 exhibited different biological processes and signaling pathways. Inflammation, oxidative damage, apoptosis, and inflammation-related signaling pathways were enriched on POD1/12. Inflammation, chemokine activity, and downstream signaling regulated by proinflammatory cytokines, such as the MTOR signaling pathway, were enriched on POD1, while downregulation of ion channel activity, mitochondrial damage, endocytosis, MAPK and neurotrophic signaling pathways developed on POD14. Additionally, we screened key genes and candidate genes, which were verified at the transcriptional and translational levels. Our results suggest that the initiation and maintenance of HNP are regulated by different molecular mechanisms. Therefore, our research may yield a fresh and deeper understanding of the mechanisms underlying HNP, providing accurate molecular targets for HNP therapy.
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This work was supported by Natural Science Foundation of Zhejiang Province (LY22H090008).
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WZ was responsible for the study conception and design. JH constructed HNP model and performed analyses of RNA sequencing data. YH and CBB contributed to behavioral experiments, zootomy and material preparation. Molecular experiments were performed by JH and FL. DW supervised the entire experiment process. The first draft of the manuscript was written by JH and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Supplementary file1 (DOCX 4299 KB) Supplementary Information The RNA-seq data that support the findings of this study are available from https://www.ncbi.nlm.nih.gov/sra/PRJNA738547. Other original data are available at https://doi.org/10.6084/m9.figshare.14797809. The software and websites involved are noted in the article.
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Huang, J., Lin, F., Hu, Y. et al. From Initiation to Maintenance: HIV-1 Gp120-induced Neuropathic Pain Exhibits Different Molecular Mechanisms in the Mouse Spinal Cord Via Bioinformatics Analysis Based on RNA Sequencing. J Neuroimmune Pharmacol 17, 553–575 (2022). https://doi.org/10.1007/s11481-021-10044-1
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DOI: https://doi.org/10.1007/s11481-021-10044-1