海南医科大学学报2026，Vol.32Issue(3)：179-187,9.DOI:10.13210/j.cnki.jhmu.20250208.003
急性低氧调控肝细胞线粒体碳代谢通路关键基因的筛选与机制研究
Screening and mechanistic study of key genes regulating the mitochondrial carbon metabolism pathway in hepatocytes under acute hypoxia
摘要
Abstract
Objective:To explore key genes and the regulatory mechanisms in the mitochondrial carbon metabolism pathway of hepatocytes under acute hypoxic exposure,using bioinformatics approaches.Methods:The human liver cell line HL7702 was cultured under normoxic conditions(95%air and 5%CO2)and hypoxic conditions(1%O2,94%N2,and 5%CO2)in separate incubators.After 24 hours of cultivation,RNA was extracted to prepare expression profile gene chips.The differential genes ob-tained from microarray experiments were integrated with a mitochondrial database for analysis.GO and KEGG enrichment analy-ses were conducted on the differential genes and the intersection genes related to mitochondrial function to excavate key pathways.A protein-protein interaction network was constructed for the differential genes and intersection genes related to mitochondrial func-tion to further screen for key genes.The mouse liver cell line AML12 was used to model hypoxia and validate the selected key genes and those involved in key mitochondrial pathways.Results:Compared to the normoxic group,the hypoxic group identified a total of 47 958 non-significant differential genes and 1 437 differential genes,among which 864 genes were upregulated and 573 genes were downregulated.KEGG enrichment analysis of the differential genes significantly enriched in metabolic pathways,ami-no acid synthesis,carbon metabolism,and coenzyme biosynthesis pathways.KEGG enrichment analysis of the intersection genes related to mitochondrial function found that they were mainly enriched in pathways such as carbon metabolism.In the protein-protein interaction(PPI)network,two key genes,FH and HSPD1,were identified,and it was found that the mRNA and protein expression levels of FH and HSPD1 were significantly upregulated under acute hypoxia.KEGG enrichment analysis,which was common to both differential genes and intersection genes related to mitochondrial function,revealed that acute hypoxia affects the expression of genes in the mitochondrial carbon metabolism pathway,including GCSH,AGXT,FH,GPT2,IDH2,and HIBCH.Conclusion:Acute hypoxia stress regulates mitochondrial function in liver tissue by upregulating FH and HSPD1 and affects the expression of GCSH,AGXT,FH,GPT2,IDH2,and HIBCH genes in the mitochondrial carbon metabolism pathway to cope with acute hypoxic exposure.These findings provide new insights for further understanding of liver cell-related dis-eases under acute hypoxia conditions.关键词
急性低氧/线粒体/碳代谢/生物信息学Key words
Acute hypoxia/Mitochondria/Carbon metabolism/Bioinformatics分类
医药卫生引用本文复制引用
李俊秀,台艳奇,邓钊红,徐金芳,胥瑾..急性低氧调控肝细胞线粒体碳代谢通路关键基因的筛选与机制研究[J].海南医科大学学报,2026,32(3):179-187,9.基金项目
This study was supported by the National Natural Science Foundation of China(82360333) （82360333）
Science and Technology Plan Project of Qinghai Province(2023-ZJ-792) 国家自然科学基金(82360333) （2023-ZJ-792）
青海省科技计划项目(2023-ZJ-792) （2023-ZJ-792）
