Psoriatic epidermis expresses high level of inflammatory mediators and the CDK2/4 cyclin‐dependent kinases are involved in the regulation of cell‐cycle progression in epidermal cells

Gesser, Borbala; Rasmussen, Majken Kirkegaard

doi:10.1111/bjd.18713

Cited by 2 publications

(2 citation statements)

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“…Consistent with cyclin A2 and D1 expression, LPA significantly increased CDK2 and CDK4 expression in HaCaT cells, and ki16425 treatment significantly decreased these LPA-induced increases ( Figure 4 ). Similarly, cyclin D1, CDK2, and CDK4 expression is increased in psoriatic lesions of psoriasis patients [ 40 ]. In addition to cell cycle regulation, cyclin A2 plays a role in cytoskeletal rearrangement and cell migration [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway

Kim

Baek

et al. 2021

IJMS

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Psoriasis is a chronic inflammatory skin disease. Recently, lysophosphatidic acid (LPA)/LPAR5 signaling has been reported to be involved in both NLRP3 inflammasome activation in macrophages and keratinocyte activation to produce inflammatory cytokines, contributing to psoriasis pathogenesis. However, the effect and molecular mechanisms of LPA/LPAR signaling in keratinocyte proliferation in psoriasis remain unclear. In this study, we investigated the effects of LPAR1/3 inhibition on imiquimod (IMQ)-induced psoriasis-like mice. Treatment with the LPAR1/3 antagonist, ki16425, alleviated skin symptoms in IMQ-induced psoriasis-like mouse models and decreased keratinocyte proliferation in the lesion. It also decreased LPA-induced cell proliferation and cell cycle progression via increased cyclin A2, cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 expression and decreased p27Kip1 expression in HaCaT cells. LPAR1 knockdown in HaCaT cells reduced LPA-induced proliferation, suppressed cyclin A2 and CDK2 expression, and restored p27Kip1 expression. LPA increased Rho-associated protein kinase 2 (ROCK2) expression and PI3K/AKT activation; moreover, the pharmacological inhibition of ROCK2 and PI3K/AKT signaling suppressed LPA-induced cell cycle progression. In conclusion, we demonstrated that LPAR1/3 antagonist alleviates IMQ-induced psoriasis-like symptoms in mice, and in particular, LPAR1 signaling is involved in cell cycle progression via ROCK2/PI3K/AKT pathways in keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway

Kim

Baek

et al. 2021

IJMS

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“…[54] However, CDK2 also has prominent contributions to immunological diseases and anti-inflammatory mechanisms. Evidence suggests that CDK2 is involved in the expression of inflammatory mediators in the psoriatic epidermis and regulates the psoriatic epidermal cell cycle, [55] suggesting that modulating CDK2 is an effective strategy for treating psoriasis. [56] This information undoubtedly provides us insight into studying the control of monkeypox.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and bioinformatics to identify molecular mechanisms and therapeutic targets of Ruyi Jinhuang Powder in the treatment of monkeypox

Zhang

et al. 2023

Medicine

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Monkeypox outbreaks across the globe has aroused widespread concern. Ruyi Jinhuang Powder (RJP), a common formula in Chinese medicine, is used to treat pox-like illnesses. This study aimed to identify the molecular mechanisms and therapeutic targets of RJP for the treatment of monkeypox using network pharmacology and bioinformatics techniques. The bioactive substances and potential targets of each component of RJP were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The differentially expressed genes (DEGs) of the monkeypox virus (MPXV) were identified from the GSE24125 by GEO2R. Key signaling pathways, bioactive components, and potential targets were obtained by bioinformatics analysis, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), disease ontology (DO), and protein-protein interactions (PPI) analyses. Finally, molecular docking was used to predict the interaction between active compounds and core targets. A total of 158 active ingredients and 17 drug-disease-shared targets of RJP were screened. Bioinformatics indicated that wogonin and quercetin might be potential drug candidates. Potential therapeutic targets were identified. Immune-related mechanisms that exerted antiviral effects included signaling pathways like TNF, age-rage, and c-type lectin receptor pathways. Our results illustrated the good therapeutic effect of RJP on monkeypox in terms of biological activity, potential targets, and molecular mechanism. This also offered a promising strategy to reveal the scientific basis and therapeutic mechanism of herbal formulas used to treat the disease.

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Psoriatic epidermis expresses high level of inflammatory mediators and the CDK2/4 cyclin‐dependent kinases are involved in the regulation of cell‐cycle progression in epidermal cells

Abstract: Linked Article: Henri et al. Br J Dermatol 2020; 182:678–689.

Cited by 2 publications

References 9 publications

Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway

Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway

Network pharmacology and bioinformatics to identify molecular mechanisms and therapeutic targets of Ruyi Jinhuang Powder in the treatment of monkeypox

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