Hu Maoting, Yu Kunlin, Wang Chunlin, Liu Wuling, Hu Anling, Kuang Yi, Gajendran Babu, Zacksenhaus Eldad, Sartori Giulio, Bertoni Francesco, Xiao Xiao, Ben-David Yaacov
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, People's Republic of China.
The Natural Products Research Center of Guizhou Province, Guiyang, Guizhou, People's Republic of China.
J Inflamm Res. 2025 Mar 20;18:4213-4231. doi: 10.2147/JIR.S500822. eCollection 2025.
Plaque psoriasis is an inflammatory skin disorder affecting nearly 2% of the world population. Despite recent advances in psoriasis treatment, there is still a need for more effective therapies. The ETS transcription factor FLI1 plays critical roles in hematopoiesis, angiogenesis, immunity, and cancer. Emerging evidence suggests that FLI1 is intricately involved in inflammatory processes underlying psoriasis pathogenesis.
RNAseq and bioinformatic analysis were used to identify the correlation between FLI1 levels and the expression of inflammatory genes associated with psoriasis. Over-expression of FLI1 in skin cells determined FLI1's role in inducing transcription of psoriasis-related inflammatory genes, including IL6, IL1A, IL1B, IL23, and TNFα. Inhibitors such as chelerythrine (CLT) were tested for their suppressive effects on these genes. Mouse models of plaque psoriasis were employed to assess the therapeutic potential of CLT and tacrolimus (TAC).
Over-expression of FLI1 in skin cells upregulated 24 psoriasis-associated genes, which were identified through RNAseq. Inhibitors of FLI1, such as CLT, suppressed these inflammatory genes in skin cells. In mouse models of plaque psoriasis induced by imiquimod (IMQ) or phorbol ester (TPA), treatment with the anti-FLI1 inhibitor CLT, administered either peritoneally or topically, significantly downregulated inflammatory genes and alleviated psoriasis symptoms. Similarly, TAC, a common immunosuppressive agent, effectively attenuated IMQ-induced psoriasis by acting as a potent anti-FLI1 compound.
These findings demonstrate that FLI1 plays a central role in psoriasis development and highlight it as a potential therapeutic target for this skin disorder.
斑块状银屑病是一种炎症性皮肤病，影响着全球近2%的人口。尽管银屑病治疗最近取得了进展，但仍需要更有效的疗法。ETS转录因子FLI1在造血、血管生成、免疫和癌症中发挥关键作用。新出现的证据表明，FLI1与银屑病发病机制中的炎症过程密切相关。
使用RNA测序和生物信息学分析来确定FLI1水平与银屑病相关炎症基因表达之间的相关性。在皮肤细胞中过表达FLI1，以确定FLI1在诱导银屑病相关炎症基因转录中的作用，这些基因包括IL6、IL1A、IL1B、IL23和TNFα。测试了白屈菜红碱（CLT）等抑制剂对这些基因的抑制作用。采用斑块状银屑病小鼠模型评估CLT和他克莫司（TAC）的治疗潜力。
通过RNA测序确定，皮肤细胞中FLI1的过表达上调了24个银屑病相关基因。FLI1抑制剂，如CLT，可抑制皮肤细胞中的这些炎症基因。在咪喹莫特（IMQ）或佛波酯（TPA）诱导的斑块状银屑病小鼠模型中，腹膜内或局部给予抗FLI1抑制剂CLT治疗，可显著下调炎症基因并减轻银屑病症状。同样，常见的免疫抑制剂TAC作为一种有效的抗FLI1化合物，可有效减轻IMQ诱导的银屑病。
这些发现表明，FLI1在银屑病发展中起核心作用，并突出其作为这种皮肤病潜在治疗靶点的地位。
