Han Ying-Hao, Feng Lin, Lee Seung-Jae, Zhang Yong-Qing, Wang Ai-Guo, Jin Mei-Hua, Sun Hu-Nan, Kwon Taeho
College of Life Science and Technology, Heilongjiang Bayi Agricultural University, 163319, Daqing, Heilongjiang, P.R. China.
Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk, 56212, Republic of Korea.
Cell Death Discov. 2023 Jul 27;9(1):263. 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 HO-induced apoptosis mediated by Ca 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.
银屑病是一种慢性全身性免疫介导性疾病，由角质形成细胞异常增殖、凋亡减少和过度分化引起。角质形成细胞异常导致的银屑病皮肤病变与炎症细胞产生的活性氧密切相关。过氧化物酶II（Prx II）是一种高效的抗氧化酶，在银屑病患者的皮肤组织中高表达。然而，Prx II在银屑病皮肤中的具体机械功能仍有待阐明。目前的研究表明，Prx II的缺失可减轻咪喹莫特诱导的小鼠银屑病症状，但血清炎症因子的量没有显著差异。Prx II基因敲低的HaCaT细胞对内质网通过1,4,5-三磷酸受体（IP3Rs）释放Ca介导的HO诱导的凋亡敏感，PI3K/AKT途径和磷酸化的GSK3β（Ser9）显著下调。此外，在NAC、2-APB、BAPTA-AM、SC79和LiCl处理后，Prx II基因敲低的HaCaT细胞对凋亡的敏感性明显降低。这些结果表明，Prx II通过PI3K/AKT/GSK3β信号轴调节角质形成细胞的凋亡。此外，用Prx II抑制剂Conoidin A治疗可显著减轻咪喹莫特模型小鼠的银屑病症状。这些发现对于通过调节银屑病角质形成细胞凋亡来制定治疗策略具有重要意义，Prx II抑制剂可能被开发为一种减轻银屑病症状的治疗药物。
