| Item type |
文献 / Documents(1) |
| 公開日 |
2023-08-24 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1038/s41598-023-29824-1 |
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関連名称 |
10.1038/s41598-023-29824-1 |
| 出版タイプ |
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|
出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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|
タイトル |
Urokinase-type plasminogen activator blockade ameliorates experimental colitis in mice |
| タイトル別表記 |
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その他のタイトル |
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
岡久, 稔也
佐藤, 康史
板東, 正浩
フジモト, ショウタ
マ, ベイベイ
中川, 忠彦
川口, 智之
中村, 文香
岡本, 耕一
宮本, 弘志
曽我部, 正弘
常山, 幸一
高山, 哲治
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| 抄録 |
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内容記述 |
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. |
| キーワード |
|
|
主題 |
ulcerative colitis |
| キーワード |
|
|
主題 |
urokinase-type plasminogen activator |
| キーワード |
|
|
主題 |
RANTES |
| キーワード |
|
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主題 |
DSS-induced colitis |
| 書誌情報 |
en : Scientific Reports
巻 13,
p. 2899,
発行日 2023-02-18
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20452322 |
| 出版者 |
|
|
出版者 |
Springer Nature |
| 備考 |
|
|
値 |
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。
学位授与者所属 : 徳島大学大学院医学研究科（医学専攻） |
| 権利情報 |
|
|
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/. |
| EID |
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識別子 |
394206 |
| 言語 |
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言語 |
eng |
| 報告番号 |
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学位授与番号 |
甲第3742号 |
| 学位記番号 |
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|
値 |
甲医第1578号 |
| 学位授与年月日 |
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|
学位授与年月日 |
2023-07-27 |
| 学位名 |
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|
学位名 |
博士（医学） |
| 学位授与機関 |
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学位授与機関名 |
徳島大学 |
k3742_abstract.pdf (138 KB)
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