RRC ID 67479
Author Ma Y, Yoshida T, Matoba K, Kida K, Shintani R, Piao Y, Jin J, Nishino T, Hanayama R.
Title Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA.
Journal 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.
Volume 11(1)
Pages 13471
Published 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
Human and Animal Cells 293(RCB1637) 293T(RCB2202) LM8(RCB1450) HCT116(RCB2979) EL4(RCB1641) MG6(RCB2403)