Mouse serum protects against total body irradiation-induced hematopoietic system injury by improving the systemic environment after radiation.
Reactive oxygen species (ROS) play a critical role in total body irradiation (TBI)-induced hematopoietic system injury. However, the mechanisms involved in ROS production in hematopoietic stem cells (HSCs) post TBI need to be further explored. In this study, we demonstrated that hematopoietic system injury in mice radiated with TBI was effectively alleviated when the blood circulation environment was changed via the injection of serum from non-radiated mice. Serum injection increased the survival of radiated mice and ameliorated TBI-induced hematopoietic system injury through attenuating myeloid skew, increasing HSC frequency, and promoting the reconstitution of radiated HSCs. Serum injection also decreased ROS levels in HSCs and regulated oxidative stress-related proteins. A serum proteome sequence array showed that proteins related to tissue injury and oxidative stress were regulated, and a serum-derived exosome microRNA sequence assay showed that the PI3K-Akt and Hippo signaling pathways were affected in radiated mice injected with serum from non-radiated mice. Furthermore, a significant increase in cell viability and a decrease in ROS were observed in radiated lineage-c-kit+ cells treated with serum-derived exosomes. Similarly, an improvement in the impaired differentiation of HSCs was observed in radiated mice injected with serum-derived exosomes. Taken together, our observations suggest that serum from non-radiated mice alleviates HSC injury in radiated mice by improving the systemic environment after radiation, and exosomes contribute to this radioprotective effect as important serum active component.
['Zhang|Junling|J|', 'Han|Xiaodan|X|', 'Zhao|Yu|Y|', 'Xue|Xiaolei|X|', 'Fan|Saijun|S|']
D000818:Animals D001798:Blood Proteins D004307:Dose-Response Relationship, Radiation D055354:Exosomes D005786:Gene Expression Regulation D006412:Hematopoietic Stem Cells D006413:Hematopoietic System D000090683:Hippo Signaling Pathway D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D035683:MicroRNAs D018384:Oxidative Stress D019869:Phosphatidylinositol 3-Kinases D017346:Protein Serine-Threonine Kinases D051057:Proto-Oncogene Proteins c-akt D019009:Proto-Oncogene Proteins c-kit D011837:Radiation-Protective Agents D017382:Reactive Oxygen Species D044967:Serum D015398:Signal Transduction D016019:Survival Analysis D014916:Whole-Body Irradiation
Mouse serum Reactive oxygen species Total body irradiation Hematopoietic stem cells Serum-derived exosomes Peripheral blood systemic environment