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.
摘要：
在这项研究中,我们使用独立于数据的采集-质谱(DIA-MS)分析寻常型银屑病(PsO)的血清蛋白质组.使用DIA-MS分析了7名健康对照和8名PsO患者的血清蛋白质组。加权基因共表达网络分析用于鉴定与PsO密切相关的差异表达蛋白(DEP)。还鉴定了PsO的Hub蛋白。蛋白质组学药物图谱2023用于预测候选枢纽蛋白药物。要确认候选因子的表达式，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，免疫组织化学染色，定量实时聚合酶链反应，并进行了蛋白质印迹。共有129个DEP与PsO密切相关。PsO的hub蛋白是PVRL1，FGFR1，PTPRS，CDH2,CDH1,MCAM,THY1确定了五种候选枢纽蛋白药物：恩科拉非尼，leupeptin,费地替尼,UNC0631和SCH530348。PTPRS被确定为这五种药物的常见药理学靶标。角质形成细胞PTPRS敲除促进IL-1α的增殖和表达,IL-1β,IL-23A,TNF-α,MMP9、CXCL8和S100A9。PTPRS在PsO中表达降低，和PTPRS负调控PsO。PTPRS可能通过抑制角质形成细胞增殖和炎症反应而参与PsO的发病,并且是PsO的潜在治疗靶标。
