JaLCDOI 10.18926/AMO/31845
フルテキストURL fulltext.pdf
著者 Wake, Hidenori| Mori, Shuji| Liu, Keyue| Takahashi, Hideo K.| Nishibori, Masahiro|
抄録 <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>
キーワード angiogenesis HMGB1 heparin
Amo Type Original Article
発行日 2009-10
出版物タイトル Acta Medica Okayama
63巻
5号
出版者 Okayama University Medical School
開始ページ 249
終了ページ 262
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
論文のバージョン publisher
査読 有り
Submission Path amo/vol63/iss5/5
PubMed ID 19893601
Web of Sience KeyUT 000271132000005
JaLCDOI 10.18926/AMO/31812
フルテキストURL fulltext.pdf
著者 Liu, Rui| Mori, Shuji| Wake, Hidenori| Zhang, Jiyong| Liu, Keyue| Izushi, Yasuhisa| Takahashi, Hideo K.| Peng, Bo| Nishibori, Masahiro|
抄録 <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>
キーワード RAGE HMGB1 S100A12 heparin inflammation
Amo Type Original Article
発行日 2009-08
出版物タイトル Acta Medica Okayama
63巻
4号
出版者 Okayama University Medical School
開始ページ 203
終了ページ 211
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
OAI-PMH Set 岡山大学
論文のバージョン publisher
査読 有り
Submission Path amo/vol63/iss4/6
PubMed ID 19727205
Web of Sience KeyUT 000269228400006
著者 和氣 秀徳|
発行日 2009-09-30
出版物タイトル
資料タイプ 学位論文
著者 和氣 秀徳|
発行日 2009-08-03
出版物タイトル 岡山医学会雑誌
121巻
2号
資料タイプ 学術雑誌論文
著者 劉 克約| 森 秀治| 高橋 英夫| 友野 靖子| 和気 秀徳| 菅家 徹| 佐藤 康晴| 平賀 憲人| 足立 尚登| 吉野 正| 西堀 正洋|
発行日 2008-12-01
出版物タイトル 岡山医学会雑誌
120巻
3号
資料タイプ 学術雑誌論文