Li Wen, Ze Kan, He Xufeng, Yang Lili, Zhang Huimin, Yuan Weian, Wang Wuqing
Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of TCM, 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China.
Derpartment of Surgery VIII (Dermatology and Sores), Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
Mol Med. 2025 Jun 10;31(1):225. doi: 10.1186/s10020-025-01279-2.
Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferative keratinocytes and an altered immune response. , a mechanically activated ion channel, has been implicated in various cellular processes, but its role in psoriasis pathogenesis remains unclear.
We examined expression in skin samples from psoriatic patients and healthy individuals using western blot, immunohistochemistry, and mRNA expression analyses. Subsequently, we employed knock-out (KO) mice to establish imiquimod (IMQ)-induced psoriasiform models for in vivo experiments. Additionally, we conducted in vitro experiments with -silenced human keratinocytes (HaCaT cells) to investigate the impact on keratinocyte function and the expression of inflammatory cytokines.
expression was significantly upregulated in the basal layer of psoriatic lesions compared to healthy controls. In vivo, KO mice showed attenuated psoriasis-like symptoms, reduced keratinocyte proliferation, inflammatory cell infiltration, and less Th17 cells compared to wild-type mice. Loss of in vitro inhibited keratinocyte proliferation and migration, while inducing apoptosis. Transcriptome sequencing and subsequent analyses revealed that knockdown modulates the NF-kB signaling pathway and associated inflammatory genes. The in vitro activation of NF-kB signaling was diminished by silencing in keratinocytes, resulting in decreased inflammatory cytokine and chemokine expression. Furthermore, facilitated keratinocyte-mediated CD4 + T cell differentiation into Th17 cells, a key pathogenic factor in psoriasis.
This study highlights the critical role of in psoriatic skin inflammation and suggests that may serve as a novel therapeutic target for psoriasis treatment. Our findings reveal that modulates keratinocyte proliferation, immune cell infiltration, and T cell differentiation through the NF-kB signaling pathway, contributing to the complex pathophysiology of psoriasis.
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银屑病是一种慢性炎症性皮肤病，其特征为角质形成细胞过度增殖和免疫反应改变。[某一机械激活离子通道]参与了多种细胞过程，但其在银屑病发病机制中的作用仍不清楚。
我们使用蛋白质免疫印迹法、免疫组织化学和mRNA表达分析，检测了银屑病患者和健康个体皮肤样本中的[该离子通道]表达。随后，我们采用[该离子通道]基因敲除（KO）小鼠建立咪喹莫特（IMQ）诱导的银屑病样模型进行体内实验。此外，我们对[该离子通道]沉默的人角质形成细胞（HaCaT细胞）进行了体外实验，以研究其对角质形成细胞功能和炎性细胞因子表达的影响。
与健康对照相比，银屑病皮损基底层中[该离子通道]的表达显著上调。在体内，与野生型小鼠相比，[该离子通道]基因敲除小鼠的银屑病样症状减轻，角质形成细胞增殖减少、炎性细胞浸润减少，Th17细胞也更少。体外[该离子通道]缺失抑制了角质形成细胞的增殖和迁移，同时诱导细胞凋亡。转录组测序及后续分析显示，[该离子通道]敲低调节了NF-κB信号通路及相关炎性基因。在角质形成细胞中，[该离子通道]沉默减弱了NF-κB信号通路的体外激活，导致炎性细胞因子和趋化因子表达降低。此外，[该离子通道]促进角质形成细胞介导的CD4 + T细胞分化为Th17细胞，Th17细胞是银屑病的关键致病因素。
本研究强调了[该离子通道]在银屑病皮肤炎症中的关键作用，并表明[该离子通道]可能成为银屑病治疗的新靶点。我们的研究结果表明，[该离子通道]通过NF-κB信号通路调节角质形成细胞增殖、免疫细胞浸润和T细胞分化，这对银屑病复杂的病理生理学有影响。
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