Effects of fractionated low-dose ionizing radiation on differentially expressed genes in ferroptosis of human bronchial epithelial cells
10.13491/j.issn.1004-714X.2025.03.001
- VernacularTitle:分次低剂量电离辐射对人支气管上皮细胞铁死亡中差异表达基因影响
- Author:
Min ZHANG
1
,
2
;
Lingyu ZHANG
2
;
Yashi CAI
2
;
Huixian LI
2
;
Yanting CHEN
2
;
Guanyou CHEN
2
;
Xin LAN
2
;
Changyong WEN
2
;
Weixu HUANG
2
;
Jianming ZOU
2
;
Huifeng CHEN
1
,
2
Author Information
1. School of Public Health, Shanxi Medical University, Taiyuan 030001, China
2. Guangdong Province Hospital forOccupational Disease Prevention and Treatment, Guangzhou 510300, China.
- Publication Type:OriginalArticles
- Keywords:
Low-dose ionizing radiation;
Human bronchial epithelial cell;
Ferroptosis;
High-throughput sequencing
- From:
Chinese Journal of Radiological Health
2025;34(3):310-317
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of fractionated low-dose ionizing radiation (LDIR) on the ferroptosis in human bronchial epithelial (HBE) cells as well as the associated differentially expressed genes (DEGs), biological processes, and signaling pathways. Methods HBE cells were exposed to different single doses of X-ray irradiation (0, 25, 50, 75, and 100 mGy) for 24, 48, and 72 h, respectively. The change in cell viability was detected by MTT assay. Cells were irradiated with 0, 25, 50, and 100 mGy X-rays 5 times, with 48 h between each irradiation and a dose rate of 50 mGy/min. Cells were harvested 24 h after irradiation for the measurement of the expression of ferroptosis-related genes SLC7A11 and GPX4 at the mRNA and protein levels, cellular iron content, and the expression of FTH1 and FTL mRNAs. High-throughput sequencing was used to screen for the DEGs in each dose group, followed by Gene Ontology-Biological Process (GO-BP) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Results Compared with the control group, single-dose LDIR significantly increased cell proliferation at 75 mGy after 24 h (P < 0.05), at 50, 75, and 100 mGy after 48 h (P < 0.05), and at 75 and 100 mGy after 72 h (P < 0.05). Compared with the control group, at the end of the fifth fractionated LDIR, SLC7A11 and GPX4 mRNAs decreased at all doses (P < 0.05), SLC7A11 protein decreased at all doses, GPX4 protein decreased at 25 and 100 mGy, iron content increased at all doses, and FTH1 and FTL mRNAs decreased at all doses (P< 0.05). Sequencing analysis identified 248, 30, and 291 DEGs and 10, 2, and 9 ferroptosis-associated genes at the three doses compared to the control. Gene Ontology-Biological Process analysis showed that DEGs were mainly enriched in biological processes such as response to lipids, cell death, and response to unfolded proteins. Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were mainly enriched in the JAK-STAT signaling pathway, lipids and atherosclerosis, ferroptosis, protein processing in the endoplasmic reticulum, and FoxO signaling pathway. Gene set enrichment analysis showed that DEGs were mainly enriched in ferroptosis, fatty acid degradation, and glutathione metabolism. Conclusion Fractionated low-dose radiation induced ferroptosis in HBE cells, and DEGs were predominantly enriched in biological processes and signaling pathways related to inflammation, ferroptosis, and endoplasmic reticulum stress.
