Mechanisms of ionizing radiation-induced pyroptosis in human intestinal epithelial cells
10.7644/j.issn.1674-9960.2024.04.001
- VernacularTitle:电离辐射诱导人肠上皮细胞焦亡机制
- Author:
Qiong WANG
1
,
2
;
Jian HONG
;
Jin GUO
;
Junzhao DUAN
;
Kexin DING
;
Fumin TAI
;
Xiaofei ZHENG
;
Changhui GE
Author Information
1. 安徽医科大学基础医学院,合肥 230032
2. 军事科学院军事医学研究院放射生物学北京市重点实验室,北京 100850
- Keywords:
pyroptosis;
ionizing radiation;
RNA-seq;
gasdermin;
intestinal cells
- From:
Military Medical Sciences
2024;48(4):241-250
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.
