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Although its pathogenesis has not been fully elucidated, recent studies have suggested that damage-associated molecular patterns (DAMPs) are mediators of remote organ injury in sterile inflammation. The purpose of this study was to investigate the possible involvement of DAMPs, including the nuclear proteins high-mobility group box 1 (HMGB1) and histone H3, in the pathogenesis of skeletal muscle I/R injury in mice.\nMethods: Hindlimb ischemia was induced in mice through bilateral ligation of inguinal regions using rubber grommets. Reperfusion was induced by cutting the rubber grommets after 2–12 h of ischemic period. Survival rates, localization of HMGB1 and histone H3 in the gastrocnemius muscle, and circulating HMGB1 and histone H3 levels were analyzed. 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  1. 医歯学総合研究科
  2. 医歯学総合研究科・博士論文

Differential Regulation of Damage-Associated Molecular Pattern Release in a Mouse Model of Skeletal Muscle Ischemia/Reperfusion Injury

http://hdl.handle.net/10232/00031970
http://hdl.handle.net/10232/00031970
2cb33707-60c7-4f87-95db-0c48fa7c5416
名前 / ファイル ライセンス アクション
Diss_古別府_裕明_ISK632_2021.pdf Diss_古別府_裕明_ISK632_2021 (7.9 MB)
license.icon
Abstract_古別府_裕明_4514810237_2021.pdf Abstract_古別府_裕明_4514810237_2021 (105.6 kB)
Result_Furubeppu_Hiroaki_isk_632.pdf Result_Furubeppu_Hiroaki_isk_632 (114.7 kB)
Comments_Furubeppu_Hiroaki_isk_632.pdf Comments_Furubeppu_Hiroaki_isk_632 (53.6 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2022-05-25
タイトル
タイトル Differential Regulation of Damage-Associated Molecular Pattern Release in a Mouse Model of Skeletal Muscle Ischemia/Reperfusion Injury
別言語のタイトル
その他のタイトル マウス骨格筋虚血再灌流障害におけるダメージ関連分子パターン放出の動向
著者 古別府, 裕明

× 古別府, 裕明

WEKO 140623

古別府, 裕明

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著者よみ
姓名 フルベップ, ヒロアキ
別言語の著者
姓名 FURUBEPPU, Hiroaki
言語
言語 eng
キーワード
主題言語 en
主題Scheme Other
主題 ischemia reperfusion injury
キーワード
主題言語 en
主題Scheme Other
主題 high mobility group box 1
キーワード
主題言語 en
主題Scheme Other
主題 extracellular histones
キーワード
主題言語 en
主題Scheme Other
主題 damage-associated molecular patterns
キーワード
主題言語 en
主題Scheme Other
主題 skeletal muscle
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
要約(Abstract)
内容記述タイプ Other
内容記述 Background: Skeletal muscle ischemia/reperfusion (I/R) injury is an important clinical issue that can cause remote organ injury. Although its pathogenesis has not been fully elucidated, recent studies have suggested that damage-associated molecular patterns (DAMPs) are mediators of remote organ injury in sterile inflammation. The purpose of this study was to investigate the possible involvement of DAMPs, including the nuclear proteins high-mobility group box 1 (HMGB1) and histone H3, in the pathogenesis of skeletal muscle I/R injury in mice.
Methods: Hindlimb ischemia was induced in mice through bilateral ligation of inguinal regions using rubber grommets. Reperfusion was induced by cutting the rubber grommets after 2–12 h of ischemic period. Survival rates, localization of HMGB1 and histone H3 in the gastrocnemius muscle, and circulating HMGB1 and histone H3 levels were analyzed. The effect of anti-HMGB1 and anti-histone H3 antibodies on survival was analyzed in mice with I/R injury.
Results: All mice with hindlimb ischemia survived for at least 36 h, while all mice died within 24 h if the hindlimbs were reperfused after ischemia for 4–12 h. Immunohistochemical analysis revealed that HMGB1 translocated from the nucleus to the cytoplasm in the ischemic gastrocnemius muscle, while histone H3 was confined to the nucleus. Accordingly, serum HMGB1 levels were significantly elevated in mice with hindlimb I/R compared with normal mice or mice with hindlimb ischemia (P < 0.05). Serum histone H3 levels were not elevated after I/R. Treatment with anti-HMGB1 antibodies significantly improved survival of mice with hindlimb I/R injury compared with control antibodies (P < 0.05).
Conclusions: HMGB1, but not histone H3, translocated to the cytoplasm during skeletal muscle ischemia, and was released into the systemic circulation after reperfusion in mice with I/R injury. Treatment with anti-HMGB1 antibodies partially improved survival.

Hiroaki Furubeppu, Takashi Ito, Midori Kakuuchi, Tomotsugu Yasuda, Chinatsu Kamikokuryo, Shingo Yamada, Ikuro Maruyama and Yasuyuki Kakihana
Differential Regulation of Damage-Associated Molecular Pattern Release in a Mouse Model of Skeletal Muscle Ischemia/Reperfusion Injury
Frontiers in Immunology 2021, 12, 628822
https://doi.org/10.3389/fimmu.2021.628822
作成日
日付 2022-02-07
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
NDC
主題Scheme NDC
主題 490
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文全文
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文要旨
ファイル(説明)
内容記述タイプ Other
内容記述 最終試験結果の要旨
ファイル(説明)
内容記述タイプ Other
内容記述 論文審査の要旨
公開者・出版者
出版者 Frontiers
公開者・出版者
出版者 鹿児島大学
公開者よみ
公開者よみ カゴシマ ダイガク
公開者別名
公開者別名 Kagoshima University
備考
備考 【指導教員:垣花泰之】
date.appl
【学位申請日】2021-12-01
学位名
学位名 博士(医学)Doctor of Philosophy in Medical Science
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 17701
学位授与機関名 鹿児島大学
学位授与年月日
学位授与年月日 2022-02-17
学位授与番号
学位授与番号 甲総研第632号
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