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Inhibiting Skp2 E3 ligase suppresses bleomycin-induced pulmonary fibrosis
http://hdl.handle.net/10271/00003502
http://hdl.handle.net/10271/00003502bcfded49-99a4-4196-bddf-3679331aa112
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (6.2 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2019-02-21 | |||||||
| タイトル | ||||||||
| タイトル | Inhibiting Skp2 E3 ligase suppresses bleomycin-induced pulmonary fibrosis | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | Skp2 | |||||||
| キーワード | ||||||||
| 主題 | E3 ligase | |||||||
| キーワード | ||||||||
| 主題 | p27 | |||||||
| キーワード | ||||||||
| 主題 | bleomycin | |||||||
| キーワード | ||||||||
| 主題 | pulmonary fibrosis | |||||||
| キーワード | ||||||||
| 主題 | mouse model | |||||||
| キーワード | ||||||||
| 主題 | chemical inhibitor | |||||||
| キーワード | ||||||||
| 主題 | idiopathic pulmonary fibrosis (IPF) | |||||||
| 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 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | E3リガーゼSkp2の阻害はブレオマイシン誘導性肺線維症を抑制する | |||||||
| 著者 |
美甘, 真史
× 美甘, 真史
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| 書誌情報 |
en : International Journal of Molecular Sciences 巻 19, 号 2, p. 474, 発行日 2018-02-06 |
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| 出版者 | ||||||||
| 出版者 | MDPI | |||||||
| 言語 | en | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and no curative therapies. SCF-Skp2 E3 ligase is a target for cancer therapy, but there have been no reports about Skp2 as a target for IPF. Here we demonstrate that Skp2 is a promising therapeutic target for IPF. We examined whether disrupting Skp2 suppressed pulmonary fibrosis in a bleomycin (BLM)-induced mouse model and found that pulmonary fibrosis was significantly suppressed in Skp2-deficient mice compared with controls. The pulmonary accumulation of fibrotic markers such as collagen type 1 and fibronectin in BLM-infused mice was decreased in Skp2-deficient mice. Moreover, the number of bronchoalveolar lavage fluid cells accompanied with pulmonary fibrosis was significantly diminished. Levels of the Skp2 target p27 were significantly decreased by BLM-administration in wild-type mice, but recovered in Skp2-/- mice. In vimentin-positive mesenchymal fibroblasts, the decrease of p27-positive cells and increase of Ki67-positive cells by BLM-administration was suppressed by Skp2-deficency. As these results suggested that inhibiting Skp2 might be effective for BLM-induced pulmonary fibrosis, we next performed a treatment experiment using the Skp2 inhibitor SZL-P1-41. As expected, BLM-induced pulmonary fibrosis was significantly inhibited by SZL-P1-41. Moreover, p27 levels were increased by the SZL-P1-41 treatment, suggesting p27 may be an important Skp2 target for BLM-induced pulmonary fibrosis. Our study suggests that Skp2 is a potential molecular target for human pulmonary fibrosis including IPF. | |||||||
| 言語 | en | |||||||
| 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 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2018-03-13 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第772号 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1422-0067 | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 29415439 | |||||||
| 出版社DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.3390/ijms19020474 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
