High-altitude hypoxia inhibits PPAR pathway induced ferroptosis in spleen of mice
10.3969/j.issn.1000-484X.2025.02.002
- VernacularTitle:高原低氧抑制PPAR通路诱导小鼠脾脏铁死亡发生
- Author:
Jiayang WANG
1
;
Ying HU
;
Yuzhen XU
;
Qifu LONG
;
Chaoqun TANG
;
Sheng YONG
Author Information
1. 青海大学基础医学部,西宁 810016;联勤保障部队第九八〇医院检验科,石家庄 050000
- Publication Type:Journal Article
- Keywords:
High-altitude hypoxia;
Spleen;
Ferroptosis;
PPAR signaling pathway
- From:
Chinese Journal of Immunology
2025;41(2):263-270
- CountryChina
- Language:Chinese
-
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.
