論文 - 詳細
| RRC ID | 67479 |
|---|---|
| 著者 | Ma Y, Yoshida T, Matoba K, Kida K, Shintani R, Piao Y, Jin J, Nishino T, Hanayama R. |
| タイトル | Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA. |
| ジャーナル | Sci Rep |
| 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. |
| 巻・号 | 11(1) |
| ページ | 13471 |
| 公開日 | 2021-6-29 |
| DOI | 10.1038/s41598-021-92860-2 |
| PII | 10.1038/s41598-021-92860-2 |
| PMID | 34188113 |
| PMC | PMC8242084 |
| MeSH | Animals Apoptosis / drug effects* Drug Evaluation, Preclinical Extracellular Vesicles / metabolism* HCT116 Cells HEK293 Cells Humans Jurkat Cells K562 Cells Mesenchymal Stem Cells / metabolism* Mice NIH 3T3 Cells Small Molecule Libraries / chemistry* Small Molecule Libraries / pharmacology* THP-1 Cells |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 24 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) 293T(RCB2202) LM8(RCB1450) HCT116(RCB2979) EL4(RCB1641) K562 Jurkat THP-1 MG6(RCB2403) |