背景:角质形成细胞(KCs)的异常生物学行为是银屑病的重要病理生理表现。铁凋亡是在存在增加的细胞内铁离子或GPX4抑制的情况下,由脂质活性氧(ROS)的积累诱导的程序性细胞死亡。
目的:本研究的目的是研究铁凋亡对寻常型银屑病角质形成细胞(KCs)生物学行为的影响及其在临床样本中的可能调控机制,细胞,和老鼠模型。
方法:我们首先检查了银屑病和正常人病变之间GPX4和4-HNE表达的差异。检测到KRT6,FLG,通过RT-qPCR在动物和细胞模型中诱导铁凋亡后的炎症细胞因子,蛋白质印迹,免疫组织化学,和流式细胞术。
结果:我们发现,在寻常型银屑病患者的皮损中,GPX4减少,氧化产物4-羟基-2-壬烯醛(HNE)增加。GPX4的表达水平与皮肤损伤的严重程度相关。此外,体外诱导Ferroptosis促进FLG的表达,降低KRT6和炎症因子的表达,减轻了体内皮肤病变的表型。
结论:我们的研究有局限性,特别是小样本量。需要更大规模的临床试验来进一步研究铁性凋亡与疾病进展之间的关系。需要更多的研究来探索铁凋亡诱导物RSL3如何在细胞和动物水平上调节KCs的异常生物学行为,并建立铁凋亡抑制剂作为对照。
结论:这项研究证实了银屑病皮损中铁性凋亡的存在,这可能与疾病严重程度成反比。铁凋亡诱导剂RSL3通过改善KCs的异常生物学行为来改善银屑病症状。
BACKGROUND: Abnormal biological behaviour of keratinocytes (KCs) is a critical pathophysiological manifestation of psoriasis. Ferroptosis is programmed cell death induced by the accumulation of lipid reactive oxygen species (ROS) in the presence of increased intracellular iron ions or inhibition of GPX4.
OBJECTIVE: The purpose of this study was to investigate the effects of ferroptosis on the biological behaviour of Keratinocytes (KCs) in psoriasis vulgaris and its possible regulatory mechanisms in clinical samples, cells, and mouse models.
METHODS: We first examined the differences in the expression of GPX4 and 4-HNE between psoriasis and normal human lesions. And detected KRT6, FLG, and inflammatory cytokines after inducing ferroptosis in animal and cell models by RT-qPCR, Western blot, immunohistochemistry, and flow cytometry.
RESULTS: We found that GPX4 was decreased and that the oxidation product 4-hydroxy-2-nonenal (HNE) was increased in the skin lesions of patients with psoriasis vulgaris. The expression level of GPX4 correlates with the severity of skin lesions. Moreover, inducing ferroptosis promoted the expression of FLG and reduced the expression of KRT6 and inflammatory cytokines in vitro, and alleviated the phenotype of skin lesions in vivo.
CONCLUSIONS: Our study has limitations, notably small sample size. Larger clinical trials are necessary to investigate the association between ferroptosis and disease progression further. More research is necessary to explore how the ferroptosis inducer RSL3 regulates the abnormal biological behaviour of KCs at both cellular and animal levels and establish ferroptosis inhibitors as controls.
CONCLUSIONS: This study confirms the existence of ferroptosis in psoriatic lesions, which may be inversely correlated with disease severity. The ferroptosis inducer RSL3 ameliorated psoriatic symptoms by improving the abnormal biological behaviour of KCs.