中国免疫学杂志2025，Vol.41Issue(2)：263-270,8.DOI:10.3969/j.issn.1000-484X.2025.02.002
高原低氧抑制PPAR通路诱导小鼠脾脏铁死亡发生
High-altitude hypoxia inhibits PPAR pathway induced ferroptosis in spleen of mice
摘要
Abstract
Objective:To explore molecular mechanism of high-altitude hypoxia regulates PPAR signaling pathway induced ferroptosis in spleen.Methods:Hypoxia animal model was constructed,target genes were screened and predicted by combination of transcriptomics and protein omics.Key genes in PPAR and ferroptosis pathways under hypoxia exposure were explored by GO and KEGG enrichment analysis and verified by RT-qPCR and Western blot.Results:Combination of transcriptomics and protein omics showed that 95 predicted target genes(protein)showed significantly differential expression under hypoxic exposure.GO annotation analysis and KEGG enrichment analysis showed that differential genes were mainly significantly enriched in PPAR and ferroptosis signaling pathways.A negative correlation was found between PPAR and ferroptosis signaling pathways,and GSEA showed that differential gene sets of PPAR and ferroptosis signaling pathways exhibited opposite expression trend in high-altitude hypoxia group.Validation of key genes PPARA,RXRB,APOA1 and SCD-1 in PPAR signaling pathway revealed that both mRNA and protein expres-sions were down-regulated under hypoxic exposure.Subsequently,differential expression was observed in mRNA and protein expres-sions of GPX4 in endogenous pathway and SLC7A11,TRP53 and TFRC in exogenous pathway in ferroptosis signaling pathway.Corre-lations between four key genes for ferroptosis and differential inflammation-associated genes(DE-IRGs)were positively or negatively.IL-1β,IL-6,IL-12,IL-18,IFN-γ and TNF-α expressions in spleen tissue were up-regulated under hypoxic exposure.Conclusion:High-altitude hypoxia exposure further induces ferroptosis through PPAR signaling pathway-mediated lipid metabolism disorders,and accompanied by occurrence of inflammatory response,which causes damage of spleen tissue.关键词
高原低氧/脾脏/铁死亡/PPAR信号通路Key words
High-altitude hypoxia/Spleen/Ferroptosis/PPAR signaling pathway分类
基础医学引用本文复制引用
王嘉阳,胡英,许玉珍,龙启福,唐超群,永胜..高原低氧抑制PPAR通路诱导小鼠脾脏铁死亡发生[J].中国免疫学杂志,2025,41(2):263-270,8.基金项目
国家自然科学基金地区科学基金(82060295) （82060295）
青海省科技计划项目基金(2023-ZJ-771) （2023-ZJ-771）
青海大学青年科研基金项目(2021-QNY-10). （2021-QNY-10）
