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01 奈良県立医科大学 >
012 大学院 >
0122 学位請求論文 >
01221 博士論文(医学) >
2023年度 >
Please use this identifier to cite or link to this item:
http://hdl.handle.net/10564/4358
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Title: | Regulation of von Willebrand factor by ADAMTS13 ameliorates lipopolysaccharide-induced lung injury in mice |
Other Titles: | ADAMTS13によるvon Willebrand因子の制御はマウスにおけるLPS誘発肺炎病態を改善する |
Authors: | Onodera, Yu Mitani, Seiji Hosoda, Chihiro Takabayashi, Yoko Sakata, Asuka Kawasaki, Ryohei Mori, Ryota Ohshima, Chiaki Nishio, Kenji Sugimoto, Mitsuhiko Soejima, Kenji Mackman, Nigel Shima, Midori Tatsumi, Kohei |
Keywords: | ADAMTS13 Inflammation Lipopolysaccharides Lung Von Willebrand factor |
Issue Date: | Dec-2023 |
Publisher: | Springer |
Citation: | International Journal of Hematology. 2023 Dec, vol.118, no.6, p.699-710 |
Abstract: | The relationship between von Willebrand factor (VWF) and inflammation has attracted considerable attention in recent years. VWF, which is stored in the Weibel-Palade bodies (WPBs) of endothelial cells (ECs), is released from WPBs in response to inflammatory stimuli and is thought to contribute to inflammation by promoting leukocyte extravasation. In this study, lung injury model mice were produced by intratracheal injection with lipopolysaccharides. The severity of lung inflammation was evaluated in mice with different genotypes (wild-type, Vwf-/-, Adamts13-/-) and mice treated with drugs that inhibit VWF function. Lung inflammation was significantly ameliorated in Vwf-/- mice compared with wild-type mice. Furthermore, inflammation was significantly suppressed in wild-type mice treated with anti-VWF A1 antibody or recombinant human ADAMTS13 compared with the untreated control group. The underlying mechanism appears to be an increased VWF/ADAMTS13 ratio at the site of inflammation and the interaction between blood cell components, such as leukocytes and platelets, and the VWF A1 domain, which promotes leukocyte infiltration into the lung. This study suggested that ADAMTS13 protein and other VWF-targeting agents may be a novel therapeutic option for treatment of pulmonary inflammatory diseases. |
Description: | 権利情報:© Japanese Society of Hematology 2023. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12185-023-03668-x |
URI: | http://hdl.handle.net/10564/4358 |
ISSN: | 0925-5710 |
DOI: | https://doi.org/10.1007/s12185-023-03668-x |
Academic Degrees and number: | 24601甲第907号 |
Degree-granting date: | 2024-03-14 |
Degree name: | 博士(医学) |
Degree-granting institutions: | 奈良県立医科大学 |
Appears in Collections: | 2023年度
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