文章基本信息

标题：Renin Promotes STAT4 Phosphorylation to Induce IL-17 Production in Keratinocytes of Oral Lichen Planus
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作者：Xuejun Ge ; Hanting Xie ; Tivoli Nguyen 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：4
页码：1-26
DOI：10.1016/j.isci.2020.100983
语种：English
出版社：Elsevier
摘要：SummaryInterleukin-17 (IL-17) is highly expressed in the epithelial layer of oral lichen planus (OLP), but the underlying mechanism for IL-17 overexpression remains unknown. Here, we identify renin that is induced by NF-κB pathway contributes to the increase of IL-17 in human oral keratinocytes (HOKs). We describe that the release of cellular renin leads to the phosphorylation of Janus kinase 2 (JAK2) protein. The phosphorylated JAK2 recruits and activates the signal transducer and activator of transcription 4 (STAT4) by phosphorylating STAT4's tyrosine residue 693 (Tyr693). The now-activated STAT4 translocates into nucleus and binds to the promoter region ofIL-17gene in HOKs. Genetic interference of renin restores IL-17 levels in OLP cell models. Collectively, our results reveal that renin upregulates IL-17 expression by enhancing STAT4 phosphorylation. This discovery unveils an underpinning by which IL-17 is increased in oral keratinocytes and provides potential targeted therapies for OLP patients.Graphical AbstractDisplay OmittedHighlights•NF-κB pathway induces renin expression in oral lichen planus•Renin upregulation promotes IL-17 expression in oral keratinocytes•Renin regulates IL-17 by promoting STAT4 phosphorylation in oral keratinocytesOral Medicine; Molecular Biology; Immunology