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Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD
https://tokushima-u.repo.nii.ac.jp/records/2011876
https://tokushima-u.repo.nii.ac.jp/records/201187613d12d0d-e58e-48e6-841c-78558a28fdf9
| 名前 / ファイル | ライセンス | アクション |
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jci_9_7_e174977.pdf (7.64 MB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||||||||||||||||||
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| 公開日 | 2024-05-02 | |||||||||||||||||||||||||||||||||
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| アクセス権 | open access | |||||||||||||||||||||||||||||||||
| 資源タイプ | ||||||||||||||||||||||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||||||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||||||||||||||||||||
| 出版社版DOI | ||||||||||||||||||||||||||||||||||
| 関連識別子 | https://doi.org/10.1172/jci.insight.174977 | |||||||||||||||||||||||||||||||||
| 関連名称 | 10.1172/jci.insight.174977 | |||||||||||||||||||||||||||||||||
| 出版タイプ | ||||||||||||||||||||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||||||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||||||||||||||||||||
| タイトル | ||||||||||||||||||||||||||||||||||
| タイトル | Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD | |||||||||||||||||||||||||||||||||
| 著者 |
ミヤザキ アンザイ, シノブ
× ミヤザキ アンザイ, シノブ
× 増田, 真志
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761
× Keenan, Audrey L.
× 塩﨑, 雄治
WEKO
1430
× Miranda, Jose G.
× ミヤザキ, マコト
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| 内容記述 | IKK2/NF-κB pathway–mediated inflammation in vascular smooth muscle cells (VSMCs) has been proposed to be an etiologic factor in medial calcification and stiffness. However, the role of the IKK2/NF-κB pathway in medial calcification remains to be elucidated. In this study, we found that chronic kidney disease (CKD) induces inflammatory pathways through the local activation of the IKK2/NF-κB pathway in VMSCs associated with calcified vascular stiffness. Despite reducing the expression of inflammatory mediators, complete inhibition of the IKK2/NF-κB pathway in vitro and in vivo unexpectedly exacerbated vascular mineralization and stiffness. In contrast, activation of NF-κB by SMC-specific IκBα deficiency attenuated calcified vascular stiffness in CKD. Inhibition of the IKK2/NF-κB pathway induced cell death of VSMCs by reducing anti–cell death gene expression, whereas activation of NF-κB reduced CKD-dependent vascular cell death. In addition, increased calcification of extracellular vesicles through the inhibition of the IKK2/NF-κB pathway induced mineralization of VSMCs, which was significantly reduced by blocking cell death in vitro and in vivo. This study reveals that activation of the IKK2/NF-κB pathway in VSMCs plays a protective role in CKD-dependent calcified vascular stiffness by reducing the release of apoptotic calcifying extracellular vesicles. | |||||||||||||||||||||||||||||||||
| 書誌情報 |
en : JCI Insight 巻 9, 号 7, p. e174977, 発行日 2024-04-08 |
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| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||||||||||||
| 収録物識別子 | 23793708 | |||||||||||||||||||||||||||||||||
| 出版者 | ||||||||||||||||||||||||||||||||||
| 出版者 | American Society for Clinical Investigation | |||||||||||||||||||||||||||||||||
| 権利情報 | ||||||||||||||||||||||||||||||||||
| 権利情報 | This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). | |||||||||||||||||||||||||||||||||
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| 識別子 | 405979 | |||||||||||||||||||||||||||||||||
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| 言語 | eng | |||||||||||||||||||||||||||||||||
