文章基本信息

标题：Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A
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作者：Shangze Gao ; Hidenori Wake ; Masakiyo Sakaguchi 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-31
DOI：10.1016/j.isci.2020.101180
语种：English
出版社：Elsevier
摘要：SummaryHigh-mobility group box-1 (HMGB1) protein has been postulated to play a pathogenic role in severe sepsis. Histidine-rich glycoprotein (HRG), a 75 kDa plasma protein, was demonstrated to improve the survival rate of septic mice through the regulation of neutrophils and endothelium barrier function. As the relationship of HRG and HMGB1 remains poorly understood, we investigated the effects of HRG on HMGB1-mediated pathway in endothelial cells, focusing on the involvement of specific receptors for HRG. HRG potently inhibited the HMGB1 mobilization and effectively suppressed rHMGB1-induced inflammatory responses and expression of all three HMGB1 receptors in endothelial cells. Moreover, we first clarified that these protective effects of HRG on endothelial cells were mediated through C-type lectin domain family 1 member A (CLEC-1A) receptor. Thus, current study elucidates protective effects of HRG on vascular endothelial cells through inhibition of HMGB1-mediated pathways may contribute to the therapeutic effects of HRG on severe sepsis.Graphical AbstractDisplay OmittedHighlights•HRG inhibited LPS-induced HMGB1 translocation and release from endothelial cells•HRG reduced inflammatory responses in endothelial cells caused by released HMGB1•CLEC-1A was identified as the receptor for the function of HRG on endothelial cellsMolecular Biology; Cell Biology