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Coagulation factor XI induces Ca2+ response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1
https://kagawa-u.repo.nii.ac.jp/records/358
https://kagawa-u.repo.nii.ac.jp/records/35805dce62e-971a-4dea-9870-baccfce2d452
| 名前 / ファイル | ライセンス | アクション |
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本文 (1.3 MB)
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内容の要旨 (57.2 kB)
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審査の結果の要旨 (546.7 kB)
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| アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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| 公開日 | 2019-04-24 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Coagulation factor XI induces Ca2+ response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1 | |||||||||||||
| 言語 | en | |||||||||||||
| 言語 | ||||||||||||||
| 言語 | eng | |||||||||||||
| 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 | |||||||||||||
| 著者 |
劉, 文華
× 劉, 文華
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Abstract Activated coagulation factor XI (FXIa) is a serine proteinase that plays a key role in the intrinsic coagulation pathway. The analysis of FXI-knockout mice has indicated the contribution of FXI to the pathogenesis of atherosclerosis. However, the underlying mechanism remains unknown. We hypothesized that FXIa exerts vascular smooth muscle effects via proteinase-activated receptor 1 (PAR1). Fura-2 fluorometry revealed that FXIa elicited intracellular Ca2+ signal in rat embryo aorta smooth muscle A7r5 cells. The influx of extracellular Ca2+ played a greater role in generating Ca2+ signal than the Ca2+ release from intracellular stores. The FXIa-induced Ca2+ signal was abolished by the pretreatment with atopaxar, an antagonist of PAR1, or 4-amidinophenylmethanesulfonyl fluoride (p-APMSF), an inhibitor of proteinase, while it was also lost in embryonic fibroblasts derived from PAR1−/− mice. FXIa cleaved the recombinant protein containing the extracellular region of PAR1 at the same site (R45/S46) as that of thrombin, a canonical PAR1 agonist. The FXIa-induced Ca2+ influx was inhibited by diltiazem, an L-type Ca2+ channel blocker, and by siRNA targeted to CaV1.2. The FXIa-induced Ca2+ influx was also inhibited by GF109203X and rottlerin, inhibitors of protein kinase C. In a wound healing assay, FXIa increased the rate of cell migration by 2.46-fold of control, which was partly inhibited by atopaxar or diltiazem. In conclusion, FXIa mainly elicits the Ca2+ signal via the PAR1/CaV1.2-mediated Ca2+ influx and accelerates the migration in vascular smooth muscle cells. The present study provides the first evidence that FXIa exerts a direct cellular effect on vascular smooth muscle. |
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| 言語 | en | |||||||||||||
| 学位名 | ||||||||||||||
| 学位名 | 博士（医学） | |||||||||||||
| 言語 | ja | |||||||||||||
| 学位授与機関 | ||||||||||||||
| 識別子Scheme | kakenhi | |||||||||||||
| 識別子 | 16201 | |||||||||||||
| 機関名 | 香川大学 | |||||||||||||
| 言語 | ja | |||||||||||||
| 機関名 | Kagawa University | |||||||||||||
| 言語 | en | |||||||||||||
| 学位授与年月日 | ||||||||||||||
| 学位授与年月日 | 2019-03-24 | |||||||||||||
| 学位授与番号 | ||||||||||||||
| 学位授与番号 | 甲第714号 | |||||||||||||
| 権利 | ||||||||||||||
| 権利情報 | Copyright © 2019 the American Physiological Society | |||||||||||||
| 言語 | en | |||||||||||||
| 論文ID（NAID） | ||||||||||||||
| 識別子タイプ | NAID | |||||||||||||
| 関連識別子 | 500001345321 | |||||||||||||
| PubMed番号 | ||||||||||||||
| 識別子タイプ | PMID | |||||||||||||
| 関連識別子 | 30566391 | |||||||||||||
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| 関連タイプ | isVersionOf | |||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | https://doi.org/10.1152/ajpcell.00426.2018 | |||||||||||||
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| 関連タイプ | isIdenticalTo | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11279134 | |||||||||||||
| 著者版フラグ | ||||||||||||||
| 出版タイプ | P | |||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | coagulation factor XI | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | proteinase-activated receptor | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | vascular smooth muscle | |||||||||||||
| KEID | ||||||||||||||
| 28677 | ||||||||||||||
