Increasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.
Humans ; Psoriasis/genetics* ; RNA, Long Noncoding/genetics*

Exanthema ; Humans ; Infant, Newborn ; Interleukins/genetics* ; Mutation ; Psoriasis/genetics*

Disease Progression ; Humans ; Pharmacogenetics ; methods ; Precision Medicine ; methods ; Psoriasis ; genetics

Psoriatic arthritis is a form of inflammatory arthritis found among patients with psoriasis, which can lead to pain, swelling or stiffness in one or more joints and even movement disorders. Epidemiological studies have shown a higher heritability for psoriatic arthritis compared with psoriasis vulgaris. With the evolvement of DNA sequencing, many genes have been associated with psoriasis vulgaris and psoriatic arthritis, which included MHC, TNF, LCE, IL23R, IL12B, TRAF3IP2 and TNFAIP3, though some, such as MHC, IL-13 and PTPN22, have been specifically associated with psoriatic arthritis. These studies have laid a foundation for risk prediction, diagnosis and drug development for psoriatic arthritis.
Arthritis, Psoriatic ; genetics ; Genetic Predisposition to Disease ; genetics ; Genetic Research ; Humans ; Polymorphism, Single Nucleotide ; genetics ; Psoriasis ; genetics

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.
Humans ; Autoimmune Diseases/genetics* ; Epigenesis, Genetic ; Lupus Erythematosus, Systemic/genetics* ; DNA Methylation ; Psoriasis/genetics*

Among over 300 genodernatoses, causative genes have been identified in 170 monogenetic diseases, while gene mapping has been performed in over 100 monogenetic and polygenctic skin diseases. Researches in genodermatoses has rapidly advanced in China in recent ten years. The causative genes involved in multiple familial trichoepithelioma and primary erythermalgia have been found. Two independent genome-wide scans with DNA markers have been performed to detect genetic linkage related to psoriasis and vitiligo. In this review article, we summarize these most recent findings.
Erythromelalgia ; genetics ; HLA Antigens ; genetics ; Humans ; NAV1.7 Voltage-Gated Sodium Channel ; Proteins ; genetics ; Psoriasis ; genetics ; Sodium Channels ; genetics ; Vitiligo ; genetics

The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.
Chromatin/genetics* ; Chromatin Assembly and Disassembly ; Gene Regulatory Networks ; Humans ; Psoriasis/genetics* ; T-Lymphocytes, Regulatory

This paper aims to explore active components and mechanism of Scutellariae Radix(SR)-Phellodendri Chinensis Cortex(PCC) drug pair in treatment of psoriasis by network pharmacology and molecular docking. Specifically, the chemical components of SR and PCC were retrieved from literature and TCMSP, as well as targets of these components from PharmMapper and UniProt, and the targets related to psoriasis from OMIM, TTD, PharmGkb, and DrugBank. Then the chemical component-medicinal target, protein-protein interaction(PPI), and chemical component-psoriasis target networks were constructed by Cytoscape. Gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed based on Metascape. Finally, molecular docking of the chemical components(high degree) with core therapeutic targets was carried out by AutoDock vina. The results showed 88 compounds of SR and PCC(including baicalin, wogonoside, berberine and phellodendrine) and 30 targets of the pair in the treatment of psoriasis. The 30 targets mainly involved the biological processes such as neutrophil mediated immunity(GO: 0002446) and T cell activation(GO: 0042110), and the signaling pathways such as metabolism of xenobiotics by cytochrome P450(hsa00980), apoptosis(hsa04210), and PI3 K-Akt signaling pathway(hsa04151). The results of molecular docking demonstrated that the main active components can spontaneously bind to the targets and the binding energy of 46 components with epidermal growth factor receptor(EGFR) was less than-8 kcal·mol~(-1). According to the PPI analysis, EGFR may be a key target for the treatment of psoriasis. Active components such as baicalin and berberine had high binding affinity with EGFR. This study preliminarily revealed the multi-component, multi-target and multi-pathway mechanism of SR-PCC drug pair in the treatment of psoriasis, which provided theoretical basis for the research on the mechanism of the drug pair in the treatment of psoriasis.
Drugs, Chinese Herbal ; Molecular Docking Simulation ; Psoriasis/genetics* ; Scutellaria baicalensis ; Signal Transduction

OBJECTIVE: To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis. METHODS: A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CD₃ were detected by immunohistochemistry; the expression level of serum interleukin (IL) -17A was detected by ELISA, and the relative expressions of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 mRNA in skin lesions were detected by real-time PCR. RESULTS: The increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group (P<0.01). The scale score, infiltration score, and total score of PASI in the moxibustion group were lower than those in the model group (P<0.01); the infiltration score and total score of PASI in the medication group were lower than those in the model group (P<0.01, P<0.05). The inflammatory cell infiltration in the model group was obvious, and the thickness of epidermal layer was increased compared with that in the normal group (P<0.01); the inflammatory cell infiltration and Munro micro abscess were decreased in the moxibustion group and the medication group, and the thickness of epidermal layer was decreased compared with that in the model group (P<0.01). Compared with the normal group, the positive cell number of PCNA and T was increased (P<0.01), and the body mass was decreased, and the spleen index was increased (P<0.01), and the expression of serum IL-17A and the relative expression of TNF-α, IL-1β and IL-6 mRNA in the skin lesions was increased in the model group (P<0.01). Compared with the model group, the positive cell number of PCNA and T was reduced (P<0.01), and the spleen index and the relative expression of TNF-α, IL-1β and IL-6 mRNA were reduced (P<0.01) in the moxibustion group and the medication group; the body mass of mice in the moxibustion group was higher than that in the model group (P<0.01); the content of serum IL-17A in the medication group was lower than that in the model group (P<0.01); the relative expression of TNF-α, IL-1β mRNA in the moxibustion group was higher than that in the medication group (P<0.01). CONCLUSION Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.
Animals ; Imiquimod ; Male ; Mice ; Moxibustion ; Psoriasis/therapy* ; Skin ; Spleen ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVES: To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line. METHODS: The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl RESULTS: HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl CONCLUSIONS Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.
Basigin ; Glucose Transporter Type 1 ; Glycolysis ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Psoriasis/genetics* ; Transcriptional Activation ; Up-Regulation