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.
en-copyright= kn-copyright= en-aut-name=LiuRui en-aut-sei=Liu en-aut-mei=Rui kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ZhangJiyong en-aut-sei=Zhang en-aut-mei=Jiyong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IzushiYasuhisa en-aut-sei=Izushi en-aut-mei=Yasuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiHideo K. en-aut-sei=Takahashi en-aut-mei=Hideo K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=PengBo en-aut-sei=Peng en-aut-mei=Bo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Shujitsu University, School of Pharmacy affil-num=3 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Shanghai University of Traditional Chinese Medicine affil-num=9 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=RAGE kn-keyword=RAGE en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=S100A12 kn-keyword=S100A12 en-keyword=heparin kn-keyword=heparin en-keyword=inflammation kn-keyword=inflammation END start-ver=1.4 cd-journal=joma no-vol=63 cd-vols= no-issue=5 article-no= start-page=249 end-page=262 dt-received= dt-revised= dt-accepted= dt-pub-year=2009 dt-pub=200910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=High mobility group box 1 complexed with heparin induced angiogenesis in a matrigel plug assay en-subtitle= kn-subtitle= en-abstract= kn-abstract=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.
en-copyright= kn-copyright= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakahashiHideo K. en-aut-sei=Takahashi en-aut-mei=Hideo K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Shujitsu University, School of Pharmacy affil-num=3 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=angiogenesis kn-keyword=angiogenesis en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=heparin kn-keyword=heparin END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=5 article-no= start-page=379 end-page=382 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201910 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histidine-rich Glycoprotein Modulates the Blood-vascular System in Septic Condition en-subtitle= kn-subtitle= en-abstract= kn-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. en-copyright= kn-copyright= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=htidine-rich glycoprotein kn-keyword=htidine-rich glycoprotein en-keyword=septic pathogenesis kn-keyword=septic pathogenesis en-keyword=immunothrombosis kn-keyword=immunothrombosis END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=3 article-no= start-page=271 end-page=277 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20081201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats kn-title=ラット中脳動脈閉塞・再灌流モデルにおける抗 HMGB1 単クローン抗体の治療効果 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name=劉克約 kn-aut-sei=劉 kn-aut-mei=克約 aut-affil-num=1 ORCID= en-aut-name=MoriShuji en-aut-sei=Mori en-aut-mei=Shuji kn-aut-name=森秀治 kn-aut-sei=森 kn-aut-mei=秀治 aut-affil-num=2 ORCID= en-aut-name=TakahashiHideo en-aut-sei=Takahashi en-aut-mei=Hideo kn-aut-name=高橋英夫 kn-aut-sei=高橋 kn-aut-mei=英夫 aut-affil-num=3 ORCID= en-aut-name=TomonoYasuko en-aut-sei=Tomono en-aut-mei=Yasuko kn-aut-name=友野靖子 kn-aut-sei=友野 kn-aut-mei=靖子 aut-affil-num=4 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name=和気秀徳 kn-aut-sei=和気 kn-aut-mei=秀徳 aut-affil-num=5 ORCID= en-aut-name=KankeToru en-aut-sei=Kanke en-aut-mei=Toru kn-aut-name=菅家徹 kn-aut-sei=菅家 kn-aut-mei=徹 aut-affil-num=6 ORCID= en-aut-name=SatoYasuharu en-aut-sei=Sato en-aut-mei=Yasuharu kn-aut-name=佐藤康晴 kn-aut-sei=佐藤 kn-aut-mei=康晴 aut-affil-num=7 ORCID= en-aut-name=HiragaNorihito en-aut-sei=Hiraga en-aut-mei=Norihito kn-aut-name=平賀憲人 kn-aut-sei=平賀 kn-aut-mei=憲人 aut-affil-num=8 ORCID= en-aut-name=AdachiNaoto en-aut-sei=Adachi en-aut-mei=Naoto kn-aut-name=足立尚登 kn-aut-sei=足立 kn-aut-mei=尚登 aut-affil-num=9 ORCID= en-aut-name=YoshinoTadashi en-aut-sei=Yoshino en-aut-mei=Tadashi kn-aut-name=吉野正 kn-aut-sei=吉野 kn-aut-mei=正 aut-affil-num=10 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name=西堀正洋 kn-aut-sei=西堀 kn-aut-mei=正洋 aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学 affil-num=4 en-affil= kn-affil=重井医学研究所 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学 affil-num=7 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 病理学（腫瘍病理） affil-num=8 en-affil= kn-affil=愛媛大学大学院 麻酔蘇生学 affil-num=9 en-affil= kn-affil=愛媛大学大学院 麻酔蘇生学 affil-num=10 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 病理学（腫瘍病理） affil-num=11 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 薬理学 en-keyword=抗体医薬 kn-keyword=抗体医薬 en-keyword=炎症 kn-keyword=炎症 en-keyword=HMGB1 kn-keyword=HMGB1 en-keyword=脳梗塞 kn-keyword=脳梗塞 en-keyword=血液脳関門 kn-keyword=血液脳関門 END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2009 dt-pub=20090930 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=HMGB1‐ヘパリン複合体はマトリゲルプラグアッセイにおいて血管新生を誘導する kn-title=High Mobility Group Box 1 Complexed with Heparin Induced Angiogenesis in a Matrigel Plug Assay en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name=和氣秀徳 kn-aut-sei=和氣 kn-aut-mei=秀徳 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=3 article-no= start-page=643 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200306 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=HMGB1 Translocation in Neurons after Ischemic Insult: Subcellular Localization in Mitochondria and Peroxisomes en-subtitle= kn-subtitle= en-abstract= kn-abstract=High mobility group box-1 (HMGB1), a nonhistone chromatin DNA-binding protein, is released from neurons into the extracellular space under ischemic, hemorrhagic, and traumatic insults. However, the details of the time-dependent translocation of HMGB1 and the subcellular localization of HMGB1 through the release process in neurons remain unclear. In the present study, we examined the subcellular localization of HMGB1 during translocation of HMGB1 in the cytosolic compartment using a middle cerebral artery occlusion and reperfusion model in rats. Double immunofluorescence microscopy revealed that HMGB1 immunoreactivities were colocalized with MTCO1(mitochondrially encoded cytochrome c oxidase I), a marker of mitochondria, and catalase, a marker of peroxisomes, but not with Rab5/Rab7 (RAS-related GTP-binding protein), LC3A/B (microtubule-associated protein 1 light chain 3), KDEL (KDEL amino acid sequence), and LAMP1 (Lysosomal Associated Membrane Protein 1), which are endosome, phagosome, endoplasmic reticulum, and lysosome markers, respectively. Immunoelectron microscopy confirmed that immune-gold particles for HMGB1 were present inside the mitochondria and peroxisomes. Moreover, HMGB1 was found to be colocalized with Drp1 (Dynamin-related protein 1), which is involved in mitochondrial fission. These results revealed the specific subcellular localization of HMGB1 during its release process under ischemic conditions. en-copyright= kn-copyright= en-aut-name=WangDengli en-aut-sei=Wang en-aut-mei=Dengli kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukuyasuYusuke en-aut-sei=Fukuyasu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TeshigawaraKiyoshi en-aut-sei=Teshigawara en-aut-mei=Kiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuLi en-aut-sei=Fu en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakeHidenori en-aut-sei=Wake en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Human Morphology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=middle cerebral artery occlusion kn-keyword=middle cerebral artery occlusion en-keyword=high-mobility group box 1 kn-keyword=high-mobility group box 1 en-keyword=subcellular localization and subcellular organelle kn-keyword=subcellular localization and subcellular organelle END