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

iScience

Masakiyo Sakaguchi¹  Hideo Takahashi²  Hui Zhong³  Youhei Takahashi³  Hidenori Wake³  Kiyoshi Teshigawara³  Dengli Wang³  Keyue Liu³  Masahiro Nishibori³  Shangze Gao³  Shuji Mori⁴ 

[1] Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan;Department of Pharmacology, Faculty of Medicine, Kindai University, Osakasayama 589-8511, Japan;Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan;Department of Pharmacology, School of Pharmacy, Shujitsu University, Okayama 703-8516, Japan;

关键词: Molecular Biology;    Cell Biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown