Article file

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.

Objectives

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.

Limitations

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.