Zheng Xuyu, Zhou Cui, Hu Yulian, Xu Shihao, Hu Li, Li Biyu, Zhao Xiaoqin, Li Qian, Tang Xin, Huang Kun
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Inflammation. 2025 Feb;48(1):89-103. doi: 10.1007/s10753-024-02044-z. Epub 2024 May 13.
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.
在本研究中，我们使用数据非依赖采集质谱法（DIA-MS）分析寻常型银屑病（PsO）患者的血清蛋白质组。使用DIA-MS分析了7名健康对照者和8例PsO患者的血清蛋白质组。采用加权基因共表达网络分析来鉴定与PsO密切相关的差异表达蛋白（DEPs）。还鉴定了PsO的枢纽蛋白。利用《2023蛋白质组学药物图谱》预测候选枢纽蛋白药物。为了证实候选因子蛋白酪氨酸磷酸酶受体S（PTPRS）在银屑病皮损和银屑病角质形成细胞模型中的表达，进行了免疫组织化学染色、定量实时聚合酶链反应和蛋白质印迹分析。共发现129种DEPs与PsO密切相关。PsO的枢纽蛋白为多聚病毒受体样蛋白1（PVRL1）、成纤维细胞生长因子受体1（FGFR1）、PTPRS、钙黏蛋白2（CDH2）、钙黏蛋白1（CDH1）、黑色素瘤细胞黏附分子（MCAM）和胸腺细胞抗原1（THY1）。鉴定出5种候选枢纽蛋白药物：恩考芬尼、亮抑酶肽、非达替尼、UNC 0631和SCH 530348。PTPRS被确定为这5种药物的共同药理学靶点。角质形成细胞中PTPRS基因敲低促进白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β）、白细胞介素-23A（IL-23A）、肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶9（MMP9）、趋化因子CXCL8和S100A9的增殖和表达。PsO患者中PTPRS表达降低，且PTPRS对PsO起负向调节作用。PTPRS可能通过抑制角质形成细胞增殖和炎症反应参与PsO的发病机制，是PsO的一个潜在治疗靶点。
