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ISG15 promotes M5-induced hacat cell proliferation through Wnt signaling in psoriasis
Xianqi Sun, Yuzhen Li, Huiwen Yu, Jiaying Lin, Chen Wang, Quanlin Liu, Bingxue Bai
2024, 4(4): 224-232. doi: 10.1515/fzm-2024-0022
Keywords: psoriasis, keratinocyte proliferation, ISG15, Wnt signaling pathway
  Objective   Psoriasis is a common chronic, recurrent, immune-mediated inflammatory skin disease, which tends to occur in cold areas. Its pathogenesis is currently unclear. This study aims to screen differentially expressed genes in the psoriasis dataset, identify the central genes, detect the expression of central genes in psoriasis lesions of patients in the cold regions and then conduct further research.   Methods   Differential genes associated with psoriasis in the GEO database were analyzed, and functional enrichment analysis and protein-protein interaction network analysis. The expression results of the identified genes were validated in psoriasis cell models. The ISG15 gene, which showed the most significant difference in expression, was further studied. The expression level of ISG15 protein in psoriasis was examined. Then, we knocked out ISG15 in psoriasis cell models and detected keratinocyte proliferation by MTT, Real-Time PCR and Western Blot. Western Blot showed the expression of β-catenin after ISG15 gene knockout.   Results   We detected the protein expression of ISG15 in the cold area of Northeast China, and found that the expression of ISG15 increased in patients with psoriasis, and the proliferation of keratinocytes and the expression of β-catenin decreased in psoriasis cell model after ISG15 was knocked down. ISG15 regulates keratinocyte proliferation through Wnt signaling pathway in psoriasis.   Conclusions   ISG15 expression is increased in psoriatic cells and skin lesions of patients with psoriasis. In psoriasis, ISG15 promotes keratinocyte proliferation through the Wnt signaling pathway.
Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population
Siyu Hao, Yu Zhang, Anqi Yin, Ying Lyu, Nannan Tong, Jiangtian Tian, Yuzhen Li
2024, 4(2): 96-101. doi: 10.1515/fzm-2024-0010
Keywords: Toll-like receptors 2, psoriasis, polymorphism, susceptibility
  Background  Psoriasis is a disease caused by genetics and immune system dysfunction, affecting the skin and joints. Toll-like receptors (TLRs) play an important role in triggering the innate immune response and controlling adaptive immunity. The role of TLR2 in the progression of psoriasis is not well understood.  Methods  A case-control study was conducted on a northern Chinese Han population, consisting of psoriasis patients and healthy control subjects. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.  Results  Four TLR2 SNPs (rs11938228, rs4696480, rs3804099, rs5743699) were genotyped and found to be in linkage disequilibrium. The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model. The haplotypes ATTC and ATCC were found to be protective against psoriasis.  Conclusion  Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.
LncRNA MIR4435-2HG promotes psoriatic inflammation via activation of PDGFRB-positive skin mesenchymal cells
Meng Tong, Guangyu Yang, Yizhou Hu, Tao Li, Yuge Gao, Yuzhen Li
2026, 6(2): 117-127. doi: 10.1515/fzm-2026-0012
Keywords: psoriasis, mesenchymal cell, MIR4435-2HG
  Background  Psoriasis is a chronic inflammatory skin disease influenced by genetic, immune, and environmental factors. Notably, its prevalence is significantly higher in colder regions, and cold climates are known to exacerbate disease symptoms. This study aimed to investigate the role of the long non-coding RNA MIR4435-2HG in regulating inflammation and cytokine production in psoriatic skin.  Methods  Single-cell RNA sequencing identified MIR4435-2HG expression in PDGFRB-positive mesenchymal cell subsets in psoriatic skin. Functional assays were performed to evaluate its effects on inflammatory cytokine expression in mesenchymal cells activated by TNF-α. An imiquimod-induced psoriasis mouse model was used to assess the effects of MIR4435-2HG knockdown in vivo.  Results  MIR4435-2HG was found to upregulate IL-6, CXCL8, and IL-17B expression in TNF-α-activated mesenchymal cells. Knockdown of MIR4435-2HG in the mouse model significantly reduced skin inflammation, epidermal hyperplasia, and psoriasis-associated cytokine expression.  Conclusion  MIR4435-2HG plays a critical role in regulating inflammation through mesenchymal cell activation, offering a potential therapeutic target for reducing psoriasis severity, especially in cold climates.