Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A

Shangze Gao, Hidenori Wake, Masakiyo Sakaguchi, Dengli Wang, Youhei Takahashi, Kiyoshi Teshigawara, Hui Zhong, Shuji Mori, Keyue Liu, Hideo Takahashi, Masahiro Nishibori

Research output: Contribution to journalArticle

Abstract

High-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.

Original languageEnglish
Article number101180
JournaliScience
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 26 2020

Keywords

  • Cell Biology
  • Molecular Biology

ASJC Scopus subject areas

  • General

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