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

Autor:	Rito Shintani, Jingchun Jin, Kazutaka Matoba, Taito Nishino, Katsuhiko Kida, Yunfei Ma, Yingshi Piao, Rikinari Hanayama, Takeshi Yoshida
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Angiogenesis THP-1 Cells Science Drug Evaluation Preclinical Apoptosis Article ESCRT Small Molecule Libraries chemistry.chemical_compound Extracellular Vesicles Jurkat Cells Mice Animals Humans Secretion Multidisciplinary Multivesicular bodies Chemistry Activator (genetics) HEK 293 cells Mesenchymal stem cell High-throughput screening Mesenchymal Stem Cells HCT116 Cells In vitro Cell biology HEK293 Cells NIH 3T3 Cells Medicine K562 Cells Obatoclax
Zdroj:	Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) Scientific Reports
ISSN:	2045-2322
Popis:	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 more desirable. However, the lack of a highly sensitive EV detection system has made the development of EV regulators difficult. We developed an ELISA system to detect EVs using TIM4 proteins, which have high affinity to phosphatidylserine and screened a 1,567-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. The three activators, cucurbitacin B, gossypol, and obatoclax, also 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 three compounds that can regulate the bioactivity of EVs.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9837ab35eb61a8b49707582789b06b46 https://doaj.org/article/2ddc367d5d854855b6999422bfd61b77 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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