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

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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.

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Funding

This work was supported by the National Natural Science Foundation of China (grant no. 81671098) and the Peking Union Medical College Innovation Fund for Graduates (grant no. 2019–1002–65).

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Contributions

Wenliang Su performed the behavioral test, immunohistochemistry, and proteomic analysis. Wenliang Su and Jiawen Yu drafted the manuscript. Lulu Ma designed this project and drafted this manuscript. Xiuhua Zhang and Yuguang Huang reviewed this manuscript and offered kind suggestions. All these authors have approved this manuscript and agreed to its publication.

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Correspondence to Lulu Ma.

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Ethics Approval

All experimental procedures were approved by the Institutional Animal Care and Use Committee of Plastic Surgery Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College and were in accordance with the guidelines provided by the National Institute of Health and the International Association for the Study of Pain.

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All authors have approved the manuscript and agreed for its publication.

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The authors declare no competing interests.

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Su, W., Yu, J., Zhang, X. et al. Proteome Profile of Trigeminal Ganglion in Murine Model of Allergic Contact Dermatitis: Complement 3 Pathway Contributes to Itch and Pain Sensation. Neurotox Res 39, 1564–1574 (2021). https://doi.org/10.1007/s12640-021-00384-4

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  • DOI: https://doi.org/10.1007/s12640-021-00384-4

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