Effect of FOXO 3 A on hematopoietic system damage in total-body irradiated mice

doi:10.3969/j. issn. 1671 -7856. 2019. 09. 002

Home > Archive>Volume 29, Issue 9, 2019 >10-16. DOI:10.3969/j. issn. 1671 -7856. 2019. 09. 002

Effect of  FOXO 3 A on hematopoietic system damage in total-body irradiated mice
DOI:
                        10.3969/j. issn. 1671 -7856. 2019. 09. 002
                    
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                        WANG Yuquan1WANG Yuquan
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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LI Chengcheng1LI Chengcheng
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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SU Lulu1SU Lulu
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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GUAN Bowen1GUAN Bowen
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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LU Yanhua1LU Yanhua
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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GUAN Feifei1GUAN Feifei
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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RONG Li2RONG Li
The Beijing Prevention and Treatment Hospital of Occupational Disease for Chemical Industry;Beijing Institute of Occupational Disease Prevention and Treatment, Beijing 100093
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WANG Xiaochun2WANG Xiaochun
The Beijing Prevention and Treatment Hospital of Occupational Disease for Chemical Industry;Beijing Institute of Occupational Disease Prevention and Treatment, Beijing 100093
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MENG Aimin1MENG Aimin
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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FAN Feiyue1FAN Feiyue
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.
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Affiliation:(1. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center,Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China.2. The Beijing Prevention and Treatment Hospital of Occupational Disease for Chemical Industry;Beijing Institute of Occupational Disease Prevention and Treatment, Beijing 100093)
Clc Number:R-33
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Abstract:

Objective To explore the effect of FOXO 3 A on hematopoietic system damage induced by irradiationexposure in FOXO 3 A-knockout mice. Methods FOXO 3 A^{-/ -} and WT mice were divided into four groups: wild-type control(WT), FOXO 3 A^{-/ -} control ( FOXO 3 A^{-/ -} ), wild-type irradiation (WT+IR), and FOXO 3 A^{-/ -} irradiation ( FOXO 3 A^{-/ -} +IR). Mice received 4 Gy X-ray total body irradiation (TBI) at a dose rate of 0. 9 Gy/ min. Fourteen days later, peripheralblood measurements, bone marrow cell counts, organ index, bone marrow cell phenotyping, and CFU-GM of hematopoieticprogenitor cells were quantified. Results Under physiological conditions, bone marrow nucleated cell counts weredecreased and proportions of hematopoietic progenitor cells (HPCs) were increased in FOXO 3 A^{-/ -} mice ( P < 0. 05). Theseresults indicate an increased decline in the proportion of HPCs/ hematopoietic stem cells (HSCs), and reduced number ofbone-marrow nucleated cells and colony forming unit-granulocyte and macrophage (CFU-GM) ( P < 0. 001) in FOXO 3 A^{-/ -}mice 14 days after 4 Gy X-ray TBI. Conclusions FOXO 3 A gene knockout damaged the homeostatic maintenance of thehematopoietic system, and aggravated HPC and HSC injury in TBI mice. The role of FOXO 3 A in regulation of hematopoietic system damage induced by radiation exposure and clinical translation remain to be further studied

Key words:ionizing radiation(IR); FOXO 3 A; hematopoietic stem cell(HSC); hematopoietic progenitor cell(HPC); reactive oxygen species(ROS); DNA damage response; mouse

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Received:May 06,2019
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Online: October 10,2019
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