NEK2 overexpression aggravates IL-22-induced keratinocyte proliferation and cytokine level increases and IMQ-induced psoriasis-like dermatitis |
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| Affiliation: | 1. Department of Dermatology, the Second Affiliated Hospital, the Domestic First-class Discipline Construction Project of Hunan University of Chinese Medicine, Changsha 410005, Hunan, China;2. Department of Dermatology, Hunan Aerospace Hospital, Changsha, Hunan, China;1. Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi''an Jiaotong University School of Health Science Center, Xi''an 710061, Shaanxi, China;2. Key Laboratory of Environmentally and Genetically Associated Diseases, Xi''an Jiaotong University School of Health Science Center, Xi''an 710061, Shaanxi, China;3. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi''an Jiaotong University School of Health Science Center, Xi''an 710061, Shaanxi, China;4. Department of Gastroenterology, The first Affiliated Hospital of Xi''an Medical University, Xi''an 710077, Shaanxi, China;5. Target Discovery Institute, NDM Research Building, Oxford Ludwig Institute of Cancer Research, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK;6. Biomedical Experimental Center, Xi''an Jiaotong University, Xi''an 710061, Shaanxi, China;1. Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;2. Center for DNA Repair and Genome Stability (CDRGS), Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;3. Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India |
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| Abstract: | BackgroundPsoriasis is a common inflammatory skin disease characterized by the excessive proliferation and abnormal differentiation of keratinocytes. Protein kinases could act on intracellular signaling pathways associated with cell proliferation.ObjectiveIdentifying more hub protein kinases affecting cellular and molecular processes in psoriasis, and exploring the dynamic effects of baicalin and NEK2 on the IL-22-induced cellular inflammation and IMQ-induced psoriasis-like mice.Methods and resultsIn this study, differentially expressed protein kinases playing a hub role in psoriasis initiation and development were identified using integrative bioinformatics analyses, and NEK2 has been chosen. NEK2 was significantly up-regulated in psoriatic samples according to online datasets and experimental analyses. In IL-22-induced cellular inflammation model in HaCaT cells, NEK2 overexpression promoted, whereas NEK2 knockdown partially abolished IL-22-induced alterations in cell viability, DNA synthesis, cytokine levels, as well as STAT3 phosphorylation and p-RB, cyclin D1, CDK4, and CDK6 protein contents. Baicalin treatment partially suppressed IL-22-induced HaCaT cell viability, DNA synthesis, and increases in cytokine levels, whereas NEK2 overexpression significantly abolished Baicalin-induced protection against cellular inflammation. In IMQ-induced psoriasis-like skin inflammation model in mice, baicalin markedly ameliorated IMQ-induced psoriasis-like symptoms and local skin inflammation, whereas NEK2 overexpression partially eliminated the therapeutic effects of baicalin.ConclusionNEK2, up-regulated in psoriatic lesion skin, could aggravate IMQ-induced psoriasis-like dermatitis and attenuate the therapeutic efficiency of baicalin through promoting keratinocyte proliferation and cytokine levels. The STAT3 signaling might be involved. |
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