WEKO3
アイテム
Arg-Gly-Asp-binding integrins activate hepatic stellate cells via the hippo signaling pathway
http://hdl.handle.net/10271/0002000483
http://hdl.handle.net/10271/0002000483b5a82c46-8439-4319-829d-c595c5078ffa
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (13.2 MB)
|
|
| Item type | 共通アイテムタイプ / Common item types(1) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2025-08-21 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Arg-Gly-Asp-binding integrins activate hepatic stellate cells via the hippo signaling pathway | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 主題 | Apoptosis | |||||||||||
| キーワード | ||||||||||||
| 主題 | Cell proliferation | |||||||||||
| キーワード | ||||||||||||
| 主題 | Focal adhesion kinase | |||||||||||
| キーワード | ||||||||||||
| 主題 | Yes-associated protein | |||||||||||
| キーワード | ||||||||||||
| 主題 | Transforming growth factor-β1 | |||||||||||
| キーワード | ||||||||||||
| 主題 | Liver fibrosis | |||||||||||
| その他のタイトル | ||||||||||||
| その他のタイトル | RGD結合インテグリンはHippo経路を介して肝星細胞を活性化する | |||||||||||
| 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 |
木次, 健介
× 木次, 健介
|
|||||||||||
| 書誌情報 |
en : Cellular Signalling 巻 99, p. 110437, 発行日 2022-08-18 |
|||||||||||
| 出版者 | ||||||||||||
| 出版者 | Elsevier | |||||||||||
| 権利 | ||||||||||||
| 権利情報 | Copyright 2022 Elsevier Inc. | |||||||||||
| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Background & aims: Liver fibrosis characterizes advanced chronic liver disease, and persistent activation of hepatic stellate cells (HSCs) is the primary cause of excessive hepatic fibrogenesis. CWHM12, an analog of the arginine-glycine-aspartic acid (RGD) amino acid sequence found in specific integrins, improves liver fibrosis; however, the detailed mechanisms remain unclear. This study aimed to clarify the cell signaling mechanisms of CWHM12 in activated HSCs. Methods: Immortalized human HSC lines, LX-2 and TWNT-1, were used to evaluate the effects of CWHM12 on intracellular signaling via the disruption of RGD-binding integrins. Results: CWHM12 strongly promoted phosphorylation and inhibited the nuclear accumulation of Yes-associated protein (YAP), which is a critical effector of the Hippo signaling pathway, leading to the inhibition of proliferation, suppression of viability, promotion of apoptosis, and induction of cell cycle arrest at the G1 phase in activated HSCs. Further investigations revealed that inhibition of TGF-β was involved in the consequences of CWHM12. Moreover, CWHM12 suppressed focal adhesion kinase (FAK) phosphorylation; consequently, Src, phosphatidylinositol 3-kinase, pyruvate dehydrogenase kinase 1, and serine-threonine kinase phosphorylation led to the translocation of YAP. These favorable effects of CWHM12 on activated HSCs were reversed by inhibiting FAK. Conclusions: These results indicate that pharmacological inhibition of RGD-binding integrins suppresses activated HSCs by blocking the Hippo signaling pathway, a cellular response which may be valuable in the treatment of hepatic fibrosis. |
|||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士（医学） | |||||||||||
| 学位の区分 | ||||||||||||
| 内容記述 | doctoral | |||||||||||
| 学位の分野 | ||||||||||||
| 内容記述 | 医学系研究科 | |||||||||||
| 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 | 13802 | |||||||||||
| 学位授与機関名 | 浜松医科大学 | |||||||||||
| 学位授与機関名 | Hamamatsu University School of Medicine | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2024-03-13 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第979号 | |||||||||||
| PISSN | ||||||||||||
| 収録物識別子 | 0898-6568 | |||||||||||
| EISSN | ||||||||||||
| 収録物識別子 | 1873-3913 | |||||||||||
| NII書誌ID (NCID) | ||||||||||||
| 収録物識別子 | AA10671314 | |||||||||||
| PubMed番号 (PMID) | ||||||||||||
| 関連識別子 | 35970425 | |||||||||||
| 出版社DOI | ||||||||||||
| 関連識別子 | https://doi.org/10.1016/j.cellsig.2022.110437 | |||||||||||
| 学位論文要旨/本文へのリンク | ||||||||||||
| 関連識別子 | http://hdl.handle.net/10271/0002000129 | |||||||||||
| 関連名称 | 学位論文要旨 | |||||||||||
| 出版タイプ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
