T-LAK细胞定向蛋白激酶（TOPK）强烈促进肿瘤细胞的恶性增殖，并被认为是肿瘤进展的标志物。银屑病是一种常见的炎症性皮肤疾病，其特征为角质形成细胞的异常增殖。然而，TOPK在银屑病中的作用尚未被很好阐明。本研究旨在调查TOPK在银屑病中的表达和作用，以及TOPK抑制剂在缓解银屑病中的作用。通过筛选源自银屑病患者和银屑病模型小鼠的基因表达数据库进行分析。收集银屑病患者的皮肤标本，进行TOPK免疫组化染色，以调查TOPK的表达和定位。接下来，建立银屑病模型小鼠，进一步确定TOPK的表达模式。然后，应用TOPK抑制剂进行研究TOPK在银屑病进展中的作用。最后，进行细胞增殖实验、凋亡实验和细胞周期分析，以探讨可能涉及的机制。我们的研究表明，TOPK在银屑病患者和银屑病模型小鼠的病变部位上调表达，并且TOPK水平与银屑病进展呈正相关。TOPK在银屑病病变中上调表达，并由表皮角质形成细胞主要表达。此外，表皮角质形成细胞中的TOPK水平与表皮增生呈正相关。此外，局部应用TOPK抑制剂OTS514明显缓解了疾病严重程度和表皮增生。在机制上，抑制TOPK可诱导角质形成细胞的G2/M期阻滞和凋亡，从而减轻表皮增生和疾病进展。总体而言，本研究发现角质形成细胞中TOPK的上调促进了银屑病的进展，而抑制TOPK有助于减轻表皮增生和银屑病的进展。© 2023 John Wiley & Sons A/S。由John Wiley & Sons Ltd.出版。

T-LAK cell-oriented protein kinase (TOPK) potently promotes malignant proliferation of tumour cells and is considered as a maker of tumour progression. Psoriasis is a common inflammatory skin disease characterized by abnormal proliferation of keratinocytes. However, the role of TOPK in psoriasis has not been well elucidated. This study aims to investigate the expression and role of TOPK in psoriasis, and the role of TOPK inhibitor in psoriasis attenuation. Gene Expression Omnibus datasets derived from psoriasis patients and psoriatic model mice were screened for analysis. Skin specimens from psoriasis patients were collected for TOPK immunohistochemical staining to investigate the expression and localization of TOPK. Next, psoriatic mice model was established to further confirm TOPK expression pattern. Then, TOPK inhibitor was applied to investigate the role of TOPK in psoriasis progression. Finally, cell proliferation assay, apoptosis assay and cell cycle analysis were performed to investigate the potential mechanism involved. Our study showed that TOPK was upregulated in the lesions of both psoriasis patients and psoriatic model mice, and TOPK levels were positively associated with psoriasis progression. TOPK was upregulated in psoriatic lesions and expressed predominantly by epidermal keratinocytes. In addition, TOPK levels in epidermal keratinocytes were positively correlated with epidermal hyperplasia. Furthermore, topical application of TOPK inhibitor OTS514 obviously alleviated disease severity and epidermal hyperplasia. Mechanismly, inhibiting TOPK induces G2/M phase arrest and apoptosis of keratinocytes, thereby attenuating epidermal hyperplasia and disease progression. Collectively, this study identifies that upregulation of TOPK in keratinocytes promotes psoriatic progression, and inhibiting TOPK attenuates epidermal hyperplasia and psoriatic progression.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.