TY - JOUR
T1 - Histidine-Rich Glycoprotein Inhibits High-Mobility Group Box-1-Mediated Pathways in Vascular Endothelial Cells through CLEC-1A
AU - Gao, Shangze
AU - Wake, Hidenori
AU - Sakaguchi, Masakiyo
AU - Wang, Dengli
AU - Takahashi, Youhei
AU - Teshigawara, Kiyoshi
AU - Zhong, Hui
AU - Mori, Shuji
AU - Liu, Keyue
AU - Takahashi, Hideo
AU - Nishibori, Masahiro
N1 - Funding Information:
This research was supported by grants from AMED (JP19 im0210109) and from the Secom Science and Technology Foundation to M.N. a Grant-in-Aid for Scientific Research (no.19H03408 to M.N.), a Grant-in-Aid for Young Scientists (no. 17K15580 to H.W.), and a Grant-in-Aid for Scientific Research (no. 19K07401 to K.T.) from the Japan Society for the Promotion of Science (JSPS). The author S.G. was supported by the scholarship from China Scholarship Council. We thank the Japanese Red Cross Society for providing the fresh-frozen human plasma. S.G. and M.N. conceived the study, designed the experiments, analyzed data, and wrote the manuscript. H.W. edited the manuscript. S.M. and H.W. purified HRG from the human plasma. H.Z. and Y.T. performed experiments on neutrophils. D.W. and K.L. produced the recombinant HMGB1. K.T. and H.T. critically reviewed the manuscript. The authors declare no competing interests.
Funding Information:
This research was supported by grants from AMED (JP19 im0210109 ) and from the Secom Science and Technology Foundation to M.N., a Grant-in-Aid for Scientific Research ( no.19H03408 to M.N.), a Grant-in-Aid for Young Scientists (no. 17K15580 to H.W.), and a Grant-in-Aid for Scientific Research (no. 19K07401 to K.T.) from the Japan Society for the Promotion of Science (JSPS). The author S.G. was supported by the scholarship from China Scholarship Council . We thank the Japanese Red Cross Society for providing the fresh-frozen human plasma.
Publisher Copyright:
© 2020 The Authors
PY - 2020/6/26
Y1 - 2020/6/26
N2 - 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.
AB - 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.
KW - Cell Biology
KW - Molecular Biology
UR - http://www.scopus.com/inward/record.url?scp=85085561657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085561657&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101180
DO - 10.1016/j.isci.2020.101180
M3 - Article
AN - SCOPUS:85085561657
SN - 2589-0042
VL - 23
JO - iScience
JF - iScience
IS - 6
M1 - 101180
ER -