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 relalionship 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. HRC 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 elueiates protective effects of HRG on vascular endothelial cells through inhintion of HMGB1-mediated pathways may contribute to the therapeutic effects of HRG on severe sepsis.
基金:
AMED [JP19 im0210109]; Secom Science and Technology Foundation [19H03408, 17K15580, 19K07401]; Japan Society for the Promotion of Science (JSPS); China Scholarship Council; Grants-in-Aid for Scientific Research [20K17930, 20H03516] Funding Source: KAKEN
第一作者机构:[1]Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pharmacol, Kita Ku, 2-5-1 Shikata Cho, Okayama 7008558, Japan
通讯作者:
通讯机构:[1]Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pharmacol, Kita Ku, 2-5-1 Shikata Cho, Okayama 7008558, Japan[*1]Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pharmacol, Kita Ku, 2-5-1 Shikata Cho, Okayama 7008558, Japan
推荐引用方式(GB/T 7714):
Gao Shangze,Wake Hidenori,Sakaguchi Masakiyo,et al.Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A[J].ISCIENCE.2020,23(6):101180.doi:10.1016/j.isci.2020.101180.
APA:
Gao, Shangze,Wake, Hidenori,Sakaguchi, Masakiyo,Wang, Dengli,Takahashi, Youhei...&Nishibori, Masahiro.(2020).Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A.ISCIENCE,23,(6)
MLA:
Gao, Shangze,et al."Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A".ISCIENCE 23..6(2020)