JaLCDOI 10.18926/AMO/57366
FullText URL 73_5_379.pdf
Author Wake, Hidenori|
Abstract Histidine-rich glycoprotein (HRG) is a 75 kDa glycoprotein synthesized in the liver whose plasma concentration is 100-150 μg/ml. HRG has been shown to modulate sepsis-related biological reactions by binding to several substances and cells, including heparin, factor XII, fibrinogen, thrombospondin, plasminogen, C1q, IgG, heme, LPS, dead cells, bacteria, and fungi. Therefore, reduction of plasma HRG levels in sepsis leads to dysregulation of coagulation, fibrinolysis, and immune response, resulting in disseminated intravascular coagulation and multiple organ failure. This review summarizes the binding and functional properties of HRG in sepsis.
Keywords htidine-rich glycoprotein septic pathogenesis immunothrombosis
Amo Type Review
Published Date 2019-10
Publication Title Acta Medica Okayama
Volume volume73
Issue issue5
Publisher Okayama University Medical School
Start Page 379
End Page 382
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2019 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 31649362
Web of Sience KeyUT 000491886600001
JaLCDOI 10.18926/AMO/31845
FullText URL fulltext.pdf
Author Wake, Hidenori| Mori, Shuji| Liu, Keyue| Takahashi, Hideo K.| Nishibori, Masahiro|
Abstract <p>Angiogenesis involves complex processes mediated by several factors and is associated with inflammation and wound healing. High mobility group box 1 (HMGB1) is released from necrotic cells as well as macrophages and plays proinflammatory roles. In the present study, we examined whether HMGB1 would exhibit angiogenic activity in a matrigel plug assay in mice. HMGB1 in combination with heparin strongly induced angiogenesis, whereas neither HMGB1 nor heparin alone showed such angiogenic activity. The heparin-dependent induction of angiogenesis by HMGB1 was accompanied by increases in the expression of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor-A120 (VEGF-A120). It is likely that the dependence of the angiogenic activity of HMGB1 on heparin was due to the efficiency of the diffusion of the HMGB1-heparin complex from matrigel to the surrounding areas. VEGF-A165 possessing a heparin-binding domain showed a pattern of heparin-dependent angiogenic activity similar to that of HMGB1. The presence of heparin also inhibited the degradation of HMGB1 by plasmin in vitro. Taken together, these results suggested that HMGB1 in complex with heparin possesses remarkable angiogenic activity, probably through the induction of TNF-alpha and VEGF-A120.</p>
Keywords angiogenesis HMGB1 heparin
Amo Type Original Article
Published Date 2009-10
Publication Title Acta Medica Okayama
Volume volume63
Issue issue5
Publisher Okayama University Medical School
Start Page 249
End Page 262
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 19893601
Web of Sience KeyUT 000271132000005
JaLCDOI 10.18926/AMO/31812
FullText URL fulltext.pdf
Author Liu, Rui| Mori, Shuji| Wake, Hidenori| Zhang, Jiyong| Liu, Keyue| Izushi, Yasuhisa| Takahashi, Hideo K.| Peng, Bo| Nishibori, Masahiro|
Abstract <p>Interaction between the receptor for advanced glycation end products (RAGE) and its ligands has been implicated in the pathogenesis of various inflammatory disorders. In this study, we establish an in vitro binding assay in which recombinant human high-mobility group box 1 (rhHMGB1) or recombinant human S100A12 (rhS100A12) immobilized on the microplate binds to recombinant soluble RAGE (rsRAGE). The rsRAGE binding to both rhHMGB1 and rhS100A12 was saturable and dependent on the immobilized ligands. The binding of rsRAGE to rhS100A12 depended on Ca2 and Zn2, whereas that to rhHMGB1 was not. Scatchard plot analysis showed that rsRAGE had higher affinity for rhHMGB1 than for rhS100A12. rsRAGE was demonstrated to bind to heparin, and rhS100A12, in the presence of Ca2, was also found to bind to heparin. We examined the effects of heparin preparations with different molecular sizesunfractionated native heparin (UFH), low molecular weight heparin (LMWH) 5000Da, and LMWH 3000Da on the binding of rsRAGE to rhHMGB1 and rhS100A12. All 3 preparations concentration-dependently inhibited the binding of rsRAGE to rhHMGB1 to a greater extent than did rhS100A12. These results suggested that heparin's anti-inflammatory effects can be partly explained by its blocking of the interaction between HMGB1 or S100A12 and RAGE. On the other hand, heparin would be a promising effective remedy against RAGE-related inflammatory disorders.</p>
Keywords RAGE HMGB1 S100A12 heparin inflammation
Amo Type Original Article
Published Date 2009-08
Publication Title Acta Medica Okayama
Volume volume63
Issue issue4
Publisher Okayama University Medical School
Start Page 203
End Page 211
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 19727205
Web of Sience KeyUT 000269228400006
Author Wake, Hidenori|
Published Date 2009-09-30
Publication Title
Content Type Thesis or Dissertation
Author Wake, Hidenori|
Published Date 2009-08-03
Publication Title 岡山医学会雑誌
Volume volume121
Issue issue2
Content Type Journal Article
Author Liu, Keyue| Mori, Shuji| Takahashi, Hideo| Tomono, Yasuko| Wake, Hidenori| Kanke, Toru| Sato, Yasuharu| Hiraga, Norihito| Adachi, Naoto| Yoshino, Tadashi| Nishibori, Masahiro|
Published Date 2008-12-01
Publication Title 岡山医学会雑誌
Volume volume120
Issue issue3
Content Type Journal Article