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アイテム
Bleomycin-Induced Pulmonary Fibrosis in Transgenic Mice Carrying the Human MUC5B rs35705950 Variant
http://hdl.handle.net/10076/0002001637
http://hdl.handle.net/10076/00020016374d0e9378-af20-4bf4-bee2-b633723749ac
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2025DM0910.pdf (21.2 MB)
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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 | 2025-11-04 | |||||||
| タイトル | ||||||||
| タイトル | Bleomycin-Induced Pulmonary Fibrosis in Transgenic Mice Carrying the Human MUC5B rs35705950 Variant | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | MUC5B | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | rs35705950 | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | pulmonary fibrosis | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | inflammation | |||||||
| 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 |
Tharavecharak, Suphachai
× Tharavecharak, Suphachai
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| 著者（ヨミ） | ||||||||
| 姓名 | タラヴェーシャラック, スパチャイ | |||||||
| 言語 | ja-Kana | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal lung disease characterized by tissue scarring and declining lung function. The MUC5B promoter polymorphism rs35705950, a significant genetic predisposition for IPF, paradoxically associates with better survival and slower disease progression than other IPF genotypes. This study investigates the potential paradoxical protective effects of this MUC5B variant in lung fibrosis. For this purpose, we developed a transgenic mouse model overexpressing the human MUC5B rs35705950 variant in the proximal large airways. Lung fibrosis was induced through subcutaneous injection of bleomycin. Results demonstrated significantly reduced lung fibrosis severity in transgenic mice compared to wild-type mice, assessed by trichrome staining, Ashcroft scoring, and hydroxyproline levels. Additionally, transgenic mice showed significantly lower levels of inflammatory cells and cytokines (TNFα, IL-6, IFNγ) and growth factors (PDGF, CTGF, IL-13) in the bronchoalveolar lavage fluid and lung tissues. There was also a significant decrease in mRNA expressions of fibrosis-related markers (periostin, fibronectin, Col1a1). In summary, this study reveals that mucin overexpression related to the MUC5B rs35705950 variant in the large airways significantly attenuates lung fibrosis and inflammatory responses in transgenic mice. These findings suggest that the rs35705950 variant modulates inflammatory and fibrotic responses in the proximal airways, which may contribute to the slower disease progression observed in IPF patients carrying this variant. Our study offers a possible explanation for the paradoxical beneficial effects of the MUC5B variant despite its role as a significant predisposing factor for IPF. | |||||||
| 言語 | en | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 本文 / Department of Immunology, Faculty and Graduate School of Medicine, Mie University | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 17p | |||||||
| 書誌情報 |
発行日 2025-09-25 |
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| DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | 10.3390/cells13181523 | |||||||
| フォーマット | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | application/pdf | |||||||
| 出版者 | ||||||||
| 出版者 | 三重大学 | |||||||
| 出版者（ヨミ） | ||||||||
| 値 | ミエダイガク | |||||||
| 学位名 | ||||||||
| 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 | 14101 | |||||||
| 学位授与機関名 | 三重大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2025-09-25 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲医学第2337号 | |||||||
| 資源タイプ（三重大） | ||||||||
| 値 | Doctoral Dissertation / 博士論文 | |||||||
