Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow

Cells

Bálint Jezsó¹  Ilona Barbara Csordás²  Eszter Persa²  Géza Sáfrány²  Rita Hargitai²  Katalin Lumniczky²  Nikolett Sándor²  Tünde Szatmári²  Katalin Balázs²  Dávid Kis²  Enikő Kis² 

[1] Doctoral School of Biology and Institute of Biology, Eötvös Loránd University, 1053 Budapest, Hungary;National Public Health Center, Department of Radiobiology and Radiohygiene, Unit of Radiation Medicine, 1097 Budapest, Hungary;

关键词: extracellular vesicles;    ionizing radiation;    bystander effects;    bone marrow;    stem cells;    miRNA;   

DOI  :  10.3390/cells11010155

来源: DOAJ

【 摘 要 】

Ionizing radiation (IR)-induced bystander effects contribute to biological responses to radiation, and extracellular vesicles (EVs) play important roles in mediating these effects. In this study we investigated the role of bone marrow (BM)-derived EVs in the bystander transfer of radiation damage. Mice were irradiated with 0.1Gy, 0.25Gy and 2Gy, EVs were extracted from the BM supernatant 24 h or 3 months after irradiation and injected into bystander mice. Acute effects on directly irradiated or EV-treated mice were investigated after 4 and 24 h, while late effects were investigated 3 months after treatment. The acute effects of EVs on the hematopoietic stem and progenitor cell pools were similar to direct irradiation effects and persisted for up to 3 months, with the hematopoietic stem cells showing the strongest bystander responses. EVs isolated 3 months after irradiation elicited no bystander responses. The level of seven microRNAs (miR-33a-3p, miR-140-3p, miR-152-3p, miR-199a-5p, miR-200c-5p, miR-375-3p and miR-669o-5p) was altered in the EVs isolated 24 hour but not 3 months after irradiation. They regulated pathways highly relevant for the cellular response to IR, indicating their role in EV-mediated bystander responses. In conclusion, we showed that only EVs from an early stage of radiation damage could transmit IR-induced bystander effects.

【 授权许可】

Unknown