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变应性接触性皮炎小鼠模型三叉神经节蛋白质组谱:补体 3 途径参与瘙痒和痛觉。

Proteome Profile of Trigeminal Ganglion in Murine Model of Allergic Contact Dermatitis: Complement 3 Pathway Contributes to Itch and Pain Sensation.

机构信息

Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Neurotox Res. 2021 Oct;39(5):1564-1574. doi: 10.1007/s12640-021-00384-4. Epub 2021 Aug 21.

DOI:10.1007/s12640-021-00384-4
PMID:34417985
Abstract

Allergic contact dermatitis (ACD) is a common inflammatory dermatosis characterized by persistent itch and pain after topical contact with reactive chemicals. Although it has been long recognized as a type-IV hypersensitivity, its complexity of pathophysiology mechanism makes it still a clinical aporia in treatment. In this study, we aimed to identify crucial proteins involved in the nociceptive sensation of ACD. Based on a chemical-induced ACD murine model, we collected trigeminal ganglions of ACD and control mice for quantitative tandem mass tag (TMT)-labeling proteomic analysis. Immunohistochemistry was further practiced to validate the bioinformatic analysis. A total of 7685 proteins were identified and analyzed. Sixty-four proteins were significantly upregulated, and 75 proteins were downregulated in ACD mice. GO analysis demonstrated that the changed proteins were significantly enriched in terms of immune and peptidase activity in ACD mice. Proteins involved in the complement and coagulation cascades were notably changed in the KEGG enrichment analysis. The upregulation of complement component 3 (C3) in trigeminal satellite cells of ACD mice was further confirmed by immunohistochemistry. ACD upregulated C3 in trigeminal satellite cells. The complement system in sensory ganglion might play an essential role in forming pruritic and nociceptive sensations in ACD.

摘要

变应性接触性皮炎(ACD)是一种常见的炎症性皮肤病,其特征是局部接触反应性化学物质后持续瘙痒和疼痛。尽管它早已被认为是一种四型超敏反应,但由于其发病机制的复杂性,在治疗上仍存在临床难题。本研究旨在鉴定参与 ACD 痛觉感知的关键蛋白。我们基于化学诱导的 ACD 小鼠模型,收集 ACD 和对照小鼠的三叉神经节进行定量串联质量标签(TMT)标记蛋白质组学分析。进一步进行免疫组织化学验证生物信息学分析。共鉴定和分析了 7685 种蛋白质。在 ACD 小鼠中,有 64 种蛋白显著上调,75 种蛋白下调。GO 分析表明,在 ACD 小鼠中,改变的蛋白在免疫和肽酶活性方面显著富集。KEGG 富集分析表明,补体和凝血级联反应中的蛋白明显改变。免疫组织化学进一步证实了 ACD 小鼠三叉神经卫星细胞中补体成分 3(C3)的上调。ACD 在三叉神经卫星细胞中上调 C3。感觉神经节中的补体系统可能在形成 ACD 的瘙痒和痛觉感知中发挥重要作用。

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