Urokinase-type plasminogen activator blockade ameliorates experimental colitis in mice

• Material Type: 博士論文
• Title: Urokinase-type plasminogen activator blockade ameliorates experimental colitis in mice
• Author/Editor: Kida, Yoshifumi; Okahisa, Toshiya; Sato, Yasushi; Bando, Masahiro; Fujimoto, Shota; Ma, Beibei; Nakagawa, Tadahiko; Kawaguchi, Tomoyuki; Nakamura, Fumika; Okamoto, Koichi; Miyamoto, Hiroshi; Sogabe, Masahiro; Tsuneyama, Koichi; Takayama, Tetsuji
• Author Heading: Kida, Yoshifumi; Okahisa, Toshiya; Sato, Yasushi; Bando, Masahiro; Fujimoto, Shota; Ma, Beibei; Nakagawa, Tadahiko; Kawaguchi, Tomoyuki; Nakamura, Fumika; Okamoto, Koichi; Miyamoto, Hiroshi; Sogabe, Masahiro; Tsuneyama, Koichi; Takayama, Tetsuji
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2023-02-18
• Publication Date (W3CDTF): 2023-02-18
• Alternative Title: 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
• Periodical title: Scientific Reports
• No. or year of volume/issue: 13
• Volume: 13
• Pages: 2899-
• ISSN (Periodical Title): ISSN : 2045-2322
• Degree grantor/type: 徳島大学
• Date Granted: 2023-07-27
• Dissertation Number: 甲第3742号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: ulcerative colitis; urokinase-type plasminogen activator; RANTES; DSS-induced colitis
• Target Audience: 一般
• Note (General): 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.
• Access Restrictions: インターネット公開
• Rights (production): 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/.
• Related Material (DOI): 10.1038/s41598-023-29824-1
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/118522/20230824104807280148/k3742_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/118522/20230824104807399028/k3742_review.pdf fulltext

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