| Guan Ziyi,Liu Mengmeng,Gao Yizhe,et al.Effects of X-ray irradiation on GATA4 expression and cellular premature senescence in human umbilical vein endothelial cells[J].Chinese Journal of Radiological Medicine and Protection,2026,46(5):490-496 |
| Effects of X-ray irradiation on GATA4 expression and cellular premature senescence in human umbilical vein endothelial cells |
| Received:May 08, 2025 |
| DOI：10.3760/cma.j.cn112271-20250508-00161 |
| KeyWords:Ionizing radiation Endothelial cells Premature senescence p62 GATA4 |
| FundProject:国家自然科学基金(31570852,82574030);北京市自然科学基金(7202139) |
| Author Name | Affiliation | E-mail | | Guan Ziyi | China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China | | | Liu Mengmeng | China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China | | | Gao Yizhe | China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China | | | Ma Liping | China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China | | | Yi Ruhan | China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China | | | Yu Nanxi | China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China | | | Gao Ling | China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China | gaoling@nirp.chinacdc.cn |
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| Abstract:: |
| Objective To investigate the effects of different doses of X-rays on senescence in human umbilical vein endothelial cells. Methods Human umbilical vein endothelial cells (EA.hy926) were collected after irradiation with 0.188, 0.375, 0.75, 2, and 4 Gy of X-rays. Cell proliferation was assessed using the CCK-8 assay kit. The proportion of senescent cells was determined via β-galactosidase staining. Western blot analysis was employed to detect changes in p21, p16, p62, and GATA4 protein expression. Real-time quantitative PCR measured mRNA expression levels of senescence-associated secretory phenotype factors IL-33, IFIT-1, and IFI-4. In vivo experiments involved whole-body irradiation of C57BL/6J mice with 2 and 4 Gy X-rays. Post-irradiation Western blot analysis assessed cardiac tissue expression of p21 and p62/GATA4. Results At 48 h after irradiation, cell proliferation was inhibited in all dose groups (t=6.07-17.10, P<0.01). At 72 h, low doses (0.188 and 0.375 Gy) promoted proliferation (t=5.52, 6.24, P<0.05), while high doses (2 and 4 Gy) inhibited proliferation (t=4.18, 3.39, P<0.01). The proportion of β-galactosidase-positive cells was significantly increased in the 2 and 4 Gy groups (t=12.34, 11.49, P<0.05). P21 protein expression was elevated in the 0.75, 2, and 4 Gy groups (t=12.66, 14.34, 17.54, P<0.05). In the 2 and 4 Gy groups, the expression of p21 and p16 proteins significantly increased 7 d after irradiation (t=3.48, 23.58, P<0.05). At 72 h after 0.375, 0.75, 2, and 4 Gy X-ray irradiation, p62 protein expression. decreased (t=9.88-51.12, P<0.05), while GATA4 protein expression increased (t=7.10-25.91, P<0.05). In the cardiac tissues of mice in the 2 and 4 Gy groups, p21 protein expression was increased (t=8.21, 12.13, P<0.05), the p62/GATA4 pathway was activated, with decreased p62 protein expression (t=11.16, 7.46, P<0.05) and increased GATA4 protein expression (t=13.66, 8.61, P<0.05). At 72 h after irradiation with different doses, mRNA expression of the SASP factor IL-33 increased in the 2 and 4 Gy groups (t=28.98, 21.17, P<0.05). In the 0.375-4 Gy groups, mRNA expression of IFIT-1 and IFI-44 increased (t=46.40-62.87, 11.28-22.07, P<0.05) Conclusions X-rays induce senescence in human umbilical vein endothelial cells and activate the p62/GATA4 pathway. |
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