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タイトル: | The identification of novel small extracellular vesicle (sEV) production modulators using luciferase‐based sEV quantification method |
著者: | Yamamoto, Aki Takahashi, Yuki https://orcid.org/0000-0002-8772-2772 (unconfirmed) Inuki, Shinsuke https://orcid.org/0000-0002-7525-1280 (unconfirmed) Nakagawa, Shumpei Nakao, Kodai Ohno, Hiroaki https://orcid.org/0000-0002-3246-4809 (unconfirmed) Doi, Masao https://orcid.org/0000-0001-6264-9217 (unconfirmed) Takakura, Yoshinobu https://orcid.org/0000-0002-7359-2647 (unconfirmed) |
著者名の別形: | 山本, 晶 高橋, 有己 井貫, 晋輔 中川, 峻平 中尾, 晃大 大野, 浩章 土居, 雅夫 髙倉, 喜信 |
キーワード: | autophagy extracellular vesicles luminescence modulators nanovesicles quantification screening |
発行日: | Sep-2022 |
出版者: | Wiley The International Society for Extracellular Vesicles |
誌名: | Journal of Extracellular Biology |
巻: | 1 |
号: | 9 |
論文番号: | e62 |
抄録: | Small extracellular vesicles (sEVs) are nano-sized vesicles secreted from various cells that contain bioactive metabolites and function as key regulators for intercellular communication. sEVs modulate diverse biological and pathological processes in the body, and the amount of circulating sEVs has been reported to correlate with certain disease progression. Therefore, the identification of small molecular compounds that can control sEV production may become a novel therapeutic strategy. In this study, a rapid, highly sensitive sEV quantification method utilizing fusion proteins consisting of Gaussia luciferase (gLuc) reporter protein and sEV markers (CD63 and CD82) was developed. A total of 480 compounds were screened to identify potent inducers and inhibitors of gLuc activity. Two novel compounds, KPYC08425 and KPYC12163, showed significant and dose-dependent changes in gLuc activity with minimal cytotoxicity based on the LDH assay. The efficacy of these two compounds was further evaluated by protein quantification of the isolated sEVs. Further evaluation of KPYC12163 suggested that the autolysosomal pathway may be involved in its inhibitory effect on sEV production. |
著作権等: | © 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/278698 |
DOI(出版社版): | 10.1002/jex2.62 |
出現コレクション: | 学術雑誌掲載論文等 |
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