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Inhibition of Src ameliorates the progression of pulmonary arterial hypertension in experimental mouse model
http://hdl.handle.net/10129/0002000720
http://hdl.handle.net/10129/0002000720e7b5e4d6-4e1b-4946-9c3e-06d8cbc03945
名前 / ファイル | ライセンス | アクション |
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Item type | リポジトリ登録用アイテムタイプ(シンプル)(1) | |||||||
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公開日 | 2024-12-25 | |||||||
タイトル | ||||||||
タイトル | Inhibition of Src ameliorates the progression of pulmonary arterial hypertension in experimental mouse model | |||||||
言語 | en | |||||||
言語 | ||||||||
言語 | eng | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Pulmonary arterial hypertension | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Src | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | endothelin | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | pulmonary artery smooth muscle cells | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | interleukin-6 | |||||||
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資源タイプ識別子(シンプル) | http://purl.org/coar/resource_type/c_db06 | |||||||
資源タイプ(シンプル) | 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 |
三浦, 尚武
× 三浦, 尚武
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抄録 | ||||||||
内容記述タイプ | Abstract | |||||||
内容記述 | Backgrounds: Pulmonary arterial hypertension (PAH) is characterized by progressive remodeling of pulmonary arterioles, resulting in right heart failure. Although currently available therapeutic agents have improved clinical outcomes of PAH patients, the efficacy remains unsatisfactory. Src, originally identified as oncogene, participates in numerous signaling pathways regulating cell survival and proliferation. However, its role in the pathogenesis of PAH is largely unknown. Methods and Results: We treated wild-type mice with monocrotaline (MCT, 600 mg/kg) or vehicle (control) once a week for eight weeks to induce PAH, and Src-specific inhibitor PP1 (4 mg/kg) was injected three times per week concurrently with MCT. Right ventricular systolic pressure was significantly higher in MCT-treated mice than in control (60.1±8.1 vs. 20.6±1.1 mmHg, p<0.0001), and PP1 attenuated the increase to 32.8±12.7 mmHg (p=0.0005). The fibrotic area in the lung was greater in MCT-treated mice than in control (14.7±0.6 vs. 5.6±2.0%, p<0.0001), and PP1 attenuated the increase to 8.9%±2.6%( p=0.02). In human pulmonary artery smooth muscle cells, endothelin increased mRNA expression of interleukin-6, and pretreatment with PP1 inhibited its increase. Conclusions: Src inhibition may attenuate the progression of PAH induced by MCT through inhibiting inflammatory cytokine production. Our results may provide a novel clinical implication for PAH treatment. |
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言語 | en | |||||||
内容記述 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | Author: Naotake Miura, Kenji Hanada, Shun Hirosawa, Hitoshi Umezaki, Yuki Konno, Kazufumi Kato, Toshihiro Iwasaki, and Hirofumi Tomita | |||||||
言語 | en | |||||||
内容記述 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | Citation: The Hirosaki Medical Journal Vol75, No.1, 31-38, 2024 | |||||||
言語 | en | |||||||
書誌情報 |
en : The Hirosaki Medical Journal 巻 75, 号 1, p. 31-38, 発行日 2024-10-30 |
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ISSN | ||||||||
収録物識別子タイプ | EISSN | |||||||
収録物識別子 | 2434-4656 | |||||||
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出版タイプ | VoR | |||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
出版者 | ||||||||
出版者 | 弘前大学出版会 | |||||||
言語 | ja | |||||||
学位名 | ||||||||
言語 | ja | |||||||
学位名 | 博士(医学) | |||||||
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 | 11101 | |||||||
言語 | ja | |||||||
学位授与機関名 | 弘前大学 | |||||||
学位授与年月日 | ||||||||
学位授与年月日 | 2024-09-30 | |||||||
学位授与番号 | ||||||||
学位授与番号 | 甲第2295号 |