Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA

Abstract Extracellular vesicles (EVs) are secreted from most cells and play important roles in cell–cell communication by transporting proteins, lipids, and nucleic acids. As the involvement of EVs in diseases has become apparent, druggable regulators of EV secretion are required. However, the lack...

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Autores principales:	Yunfei Ma, Takeshi Yoshida, Kazutaka Matoba, Katsuhiko Kida, Rito Shintani, Yingshi Piao, Jingchun Jin, Taito Nishino, Rikinari Hanayama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ddc367d5d854855b6999422bfd61b77
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spelling	oai:doaj.org-article:2ddc367d5d854855b6999422bfd61b772021-12-02T16:31:58ZIdentification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA10.1038/s41598-021-92860-22045-2322https://doaj.org/article/2ddc367d5d854855b6999422bfd61b772021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92860-2https://doaj.org/toc/2045-2322Abstract Extracellular vesicles (EVs) are secreted from most cells and play important roles in cell–cell communication by transporting proteins, lipids, and nucleic acids. As the involvement of EVs in diseases has become apparent, druggable regulators of EV secretion are required. However, the lack of a highly sensitive EV detection system has made the development of EV regulators difficult. We developed an ELISA system using a high-affinity phosphatidylserine-binder TIM4 to capture EVs and screened a 1567-compound library. Consequently, we identified one inhibitor and three activators of EV secretion in a variety of cells. The inhibitor, apoptosis activator 2, suppressed EV secretion via a different mechanism and had a broader cellular specificity than GW4869. Moreover, the three activators, namely cucurbitacin B, gossypol, and obatoclax, had broad cellular specificity, including HEK293T cells and human mesenchymal stem cells (hMSCs). In vitro bioactivity assays revealed that some regulators control EV secretion from glioblastoma and hMSCs, which induces angiogenesis and protects cardiomyocytes against apoptosis, respectively. In conclusion, we developed a high-throughput method to detect EVs with high sensitivity and versatility, and identified four compounds that can regulate the bioactivity of EVs.Yunfei MaTakeshi YoshidaKazutaka MatobaKatsuhiko KidaRito ShintaniYingshi PiaoJingchun JinTaito NishinoRikinari HanayamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yunfei Ma Takeshi Yoshida Kazutaka Matoba Katsuhiko Kida Rito Shintani Yingshi Piao Jingchun Jin Taito Nishino Rikinari Hanayama Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA
description	Abstract Extracellular vesicles (EVs) are secreted from most cells and play important roles in cell–cell communication by transporting proteins, lipids, and nucleic acids. As the involvement of EVs in diseases has become apparent, druggable regulators of EV secretion are required. However, the lack of a highly sensitive EV detection system has made the development of EV regulators difficult. We developed an ELISA system using a high-affinity phosphatidylserine-binder TIM4 to capture EVs and screened a 1567-compound library. Consequently, we identified one inhibitor and three activators of EV secretion in a variety of cells. The inhibitor, apoptosis activator 2, suppressed EV secretion via a different mechanism and had a broader cellular specificity than GW4869. Moreover, the three activators, namely cucurbitacin B, gossypol, and obatoclax, had broad cellular specificity, including HEK293T cells and human mesenchymal stem cells (hMSCs). In vitro bioactivity assays revealed that some regulators control EV secretion from glioblastoma and hMSCs, which induces angiogenesis and protects cardiomyocytes against apoptosis, respectively. In conclusion, we developed a high-throughput method to detect EVs with high sensitivity and versatility, and identified four compounds that can regulate the bioactivity of EVs.
format	article
author	Yunfei Ma Takeshi Yoshida Kazutaka Matoba Katsuhiko Kida Rito Shintani Yingshi Piao Jingchun Jin Taito Nishino Rikinari Hanayama
author_facet	Yunfei Ma Takeshi Yoshida Kazutaka Matoba Katsuhiko Kida Rito Shintani Yingshi Piao Jingchun Jin Taito Nishino Rikinari Hanayama
author_sort	Yunfei Ma
title	Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA
title_short	Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA
title_full	Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA
title_fullStr	Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA
title_full_unstemmed	Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA
title_sort	identification of small compounds regulating the secretion of extracellular vesicles via a tim4-affinity elisa
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2ddc367d5d854855b6999422bfd61b77
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Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA

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