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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
著者
喜田, 慶史 徳島大学大学院医学研究科(医学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
板東, 正浩 Tokushima University
Fujimoto, Shota Tokushima University
Ma, Beibei Tokushima University
中村, 文香 Tokushima University
キーワード
ulcerative colitis
urokinase-type plasminogen activator
RANTES
DSS-induced colitis
資料タイプ
学位論文
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.
掲載誌名
Scientific Reports
ISSN
20452322
出版者
Springer Nature
13
開始ページ
2899
発行日
2023-02-18
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/.
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
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3742号
学位記番号
甲医第1578号
学位授与年月日
2023-07-27
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系