ID | 118522 |
タイトル別表記 | ウロキナーゼ型プラスミノーゲンアクチベータの阻害はマウス実験的腸炎を改善する
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著者 |
板東, 正浩
Tokushima University
Fujimoto, Shota
Tokushima University
Ma, Beibei
Tokushima University
中村, 文香
Tokushima University
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キーワード | ulcerative colitis
urokinase-type plasminogen activator
RANTES
DSS-induced colitis
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資料タイプ |
学位論文
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抄録 | Although several angiogenesis-related factors are reportedly involved in the pathogenesis of ulcerative colitis (UC), the mechanisms by which they contribute to disease are unclear. We first examined the expression of angiogenesis-related factors in inflamed colorectal tissue of UC patients using antibody array, and identified the 5 factors with highest expression, which included matrix metalloproteinase-8, urokinase-type plasminogen activator (uPA), angiostatin/plasminogen, hepatocyte growth factor and endoglin. Subsequent real-time PCR experiments using additional colorectal tissues revealed that uPA mRNA levels were significantly higher in inflamed tissues than in non-inflamed tissues, and significantly correlated with the severity of UC. Mirror section immunohistochemistry revealed that uPA was expressed in the neutrophils of inflamed colorectal tissues. We administered dextran sulfate sodium (DSS) in drinking water to uPA knockout (uPA−/−) mice, and found that the disease activity index in uPA-/- mice was marginally lower and the histological score in uPA−/− mice was significantly lower than those in wild-type mice, suggesting the importance of uPA in colitis. When an uPA selective inhibitor, UK122, was administered to DSS-treated C57BL6J mice, the disease activity index and histological score in those mice were significantly lower compared with control mice. Multiple cytokine/chemokine assay using colorectal tissues from uPA−/− and UK122-treated mice revealed significantly lowered level of RANTES. In conclusion, uPA was highly expressed in neutrophils of the inflamed mucosa of UC patients, and the expression level correlated with the severity of UC. Genetic uPA deletion or pharmacological uPA blockade significantly ameliorated colitis in mice, concomitant with downregulation of RANTES.
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掲載誌名 |
Scientific Reports
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ISSN | 20452322
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出版者 | Springer Nature
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巻 | 13
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開始ページ | 2899
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発行日 | 2023-02-18
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Yoshifumi Kidaの学位論文として提出され,学位審査・授与の対象となっている。 |
権利情報 | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3742号
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学位記番号 | 甲医第1578号
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学位授与年月日 | 2023-07-27
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
病院
医学系
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