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Mass Spectrometry-Based Proteomics Analysis Unveils PTPRS Inhibits Proliferation and Inflammatory Response of Keratinocytes in Psoriasis

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Abstract

In this study, we used data-independent acquisition-mass spectrometry (DIA-MS) to analyze the serum proteome in psoriasis vulgaris (PsO). The serum proteomes of seven healthy controls and eight patients with PsO were analyzed using DIA-MS. Weighted gene co-expression network analysis was used to identify differentially expressed proteins (DEPs) that were closely related to PsO. Hub proteins of PsO were also identified. The Proteomics Drug Atlas 2023 was used to predict candidate hub protein drugs. To confirm the expression of the candidate factor, protein tyrosine phosphatase receptor S (PTPRS), in psoriatic lesions and the psoriatic keratinocyte model, immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blotting were performed. A total of 129 DEPs were found to be closely related to PsO. The hub proteins for PsO were PVRL1, FGFR1, PTPRS, CDH2, CDH1, MCAM, and THY1. Five candidate hub protein drugs were identified: encorafenib, leupeptin, fedratinib, UNC 0631, and SCH 530348. PTPRS was identified as a common pharmacological target for these five drugs. PTPRS knockdown in keratinocytes promoted the proliferation and expression of IL-1α, IL-1β, IL-23A, TNF-α, MMP9, CXCL8, and S100A9. PTPRS expression was decreased in PsO, and PTPRS negatively regulated PsO. PTPRS may be involved in PsO pathogenesis through the inhibition of keratinocyte proliferation and inflammatory responses and is a potential treatment target for PsO.

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Data Availability

The data presented in this study are available in the main body of the manuscript and supplementary information.

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Acknowledgements

We thank Shanghai Applied Protein Technology Co., Ltd. for their help with proteomics data acquisition.

Funding

This research was funded by the Science-Health Joint Medical Research Project of Chongqing, grant number 2020FYYX017 to KH, the National Natural Science Foundation of China, grant number 81972942 to KH, the Chongqing Innovative Support Program for Returned Overseas Chinese Scholars grant number cx2020103 to KH, and the High-level Medical Reserved Personnel Training Project of Chongqing grant number 2020GDRC028 to KH.

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  1. Xuyu Zheng and Cui Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Xuyu Zheng, Cui Zhou, Yulian Hu, Li Hu, Biyu Li, Xiaoqin Zhao, Qian Li, Xin Tang & Kun Huang

  2. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Shihao Xu

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Contributions

Kun Huang conceived and supervised the study. Xuyu Zheng, Cui Zhou, and Yulian Hu performed the literature review and drafted the manuscript. Xuyu Zheng, Shihao Xu and Xin Tang contributed to experimental data collection and analysis. Li Hu, Biyu Li, Xiaoqin Zhao, and Qian Li prepared the figures. Xuyu Zheng and Cui Zhou contributed to the critical revision of the manuscript. All authors approved the final manuscript and agreed to take responsibility for all aspects of the work.

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Zheng, X., Zhou, C., Hu, Y. et al. Mass Spectrometry-Based Proteomics Analysis Unveils PTPRS Inhibits Proliferation and Inflammatory Response of Keratinocytes in Psoriasis. Inflammation (2024). https://doi.org/10.1007/s10753-024-02044-z

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