Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis

• Published in: Cell death discovery 2023-07, Vol.9 (1), p.263-263, Article 263
• Main Authors: Han, Ying-Hao, Feng, Lin, Lee, Seung-Jae, Zhang, Yong-Qing, Wang, Ai-Guo, Jin, Mei-Hua, Sun, Hu-Nan, Kwon, Taeho
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/80/86/2366; 692/699/4033; AKT protein; Animal models; Apoptosis; Biochemistry; Biomedical and Life Sciences; Calcium (reticular); Cell Biology; Cell Cycle Analysis; Down-regulation; Endoplasmic reticulum; Hydrogen peroxide; Inflammation; Keratinocytes; Life Sciences; Lithium chloride; Peroxiredoxin; Psoriasis; Skin diseases; Skin lesions; Stem Cells
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-023-01566-z

Psoriasis is a chronic, systemic immune-mediated disease caused by abnormal proliferation, decreased apoptosis, and over-differentiation of keratinocytes. The psoriatic skin lesions due to abnormal keratinocytes are closely associated with ROS produced by inflammatory cells. Peroxiredoxin II (Prx II) is an efficient antioxidant enzyme, which were highly expressed in skin tissues of psoriasis patient. However, the detailed mechanical functions of Prx II on psoriatic skin remain to be elucidated. Present study showed that depletion of Prx II results in alleviation of symptoms of IMQ-induced psoriasis in mice, but no significant differences in the amounts of serum inflammatory factors. Prx II-knockdown HaCaT cells were susceptible to H 2 O 2 -induced apoptosis mediated by Ca 2+ release from the endoplasmic reticulum through 1,4,5-triphosphate receptors (IP3Rs), the PI3K/AKT pathway and phosphorylated GSK3β (Ser9) were significant downregulated. Additionally, significantly reduced sensitivity of Prx II-knockdown HaCaT cells to apoptosis was evident post NAC, 2-APB, BAPTA-AM, SC79 and LiCl treated. These results suggest that Prx II regulated apoptosis of keratinocytes via the PI3K/AKT/GSK3β signaling axis. Furthermore, treatment with the Prx II inhibitor Conoidin A significantly alleviated psoriatic symptoms in IMQ model mice. These findings have important implications for developing therapeutic strategies through regulate apoptosis of keratinocytes in psoriasis, and Prx II inhibitors may be exploited as a therapeutic drug to alleviate psoriatic symptoms.