The Role Of Cell Senescence In Irradiation Induced Long-term Injury Of Bone Marrow And Lung

With the development of science and technology,ionizing radiation(IR)has been widely used in energy production,medical diagnosis and treatment,and military field,and the possibility of IR exposure is increasing.Some therapeutic strategies have been used for acute injury induced by IR.Long-term injury induced by IR is easy to be ignored in clinic,and there is no effective treatment.Therefore,prevention and treatment of irradiation induced long-term injury is of great significance both in medical and military fields.Long-term myelosuppression and radiation-induced lung injury may occur after IR,but the mechanisms have yet not been clarified,which is important to be solved in the field of radiation medicine.Previous studies found cell senescence played an important role in IR-induced long-term injury.In this research,we studied new molecular mechanism of hematopoietic stem cell(HSC)senescence induced by IR,and further explored the role of senescent macrophages during radiation-induced lung injury.Exploring the mechanism of cell senescence will provide reference for prevention and treatment of irradiation induced long-term injury.In order to elucidate new molecular mechanism of HSC senescence,we screened and verified the differentially expressed genes.It had been shown that membrane-spanning 4-domains subfamily A3(Ms4a3)and Gsdme(Gasdermin E)might be related to the long-term injury of hematopoietic system after exposure to IR.Gsdme-/-mice were used to explore the effect of Gsdme deficiency on IR-induced hematopoietic system injury.We found that Gsdme deficiency had protective effects on acute injury and long-term injury of hematopoietic system,indicating that Gsdme might be a target for the prevention and treatment of radiation-induced hematopoietic injury.To explore the role of senescent macrophages in the development of radiation-induced pulmonary fibrosis(RIPF),IR-induced senescent bone marrow-derived monocytes/macrophages(BMMs)in vitro and RIPF mice were used.The results showed that IR could cause macrophages senescence and increase the secretion of senescence-associated secretory phenotype(SASP)in vitro and in vivo,which might play an important role in the progression of RIPF.These data suggested that senescent macrophages might be the targets for prevention and treatment of pulmonary fibrosis.In summary,we had found new molecular mechanism of IR-induced long-term injury of HSC,providing a new potential target for prevention and treatment of long-term injury.We also discovered the role of senescent macrophages in the process of pulmonary fibrosis,which promoted the development of research in mechanisms of RIPF.