Hypoxia at high altitude induces inflammation in the spleen of mice through NOD⁃like receptor signaling pathway
10.19405/j.cnki.issn1000-1492.2023.09.011
- Author:
Jiayang Wang
1
;
Ying Hu
1
;
Yuzhen Xu
1
;
Qifu Long
1
;
Chaoqun Tang
1
;
Sheng Yong
1
Author Information
1. Dept of Immunology , Faculty of Medicine , Qinghai University , Xining 810016
- Publication Type:Journal Article
- Keywords:
plateau hypoxia;
spleen;
metabolomics;
transcriptomics;
NOD⁃like receptor signaling pathway
- From:
Acta Universitatis Medicinalis Anhui
2023;58(9):1498-1506
- CountryChina
- Language:Chinese
-
Abstract:
Objective : Based on metabolomics and transcriptomics analysis , to explore the molecular mechanism of
spleen inflammation induced by high altitude hypoxia in mice through NOD⁃like receptor signaling pathway .
Methods :C57BL/6 mice were raised at an altitude of 400 m and 4 200 m respectively , with five mice in each group , and spleen tissues were collected after 30 days . Differential metabolites and differentially expressed genes in key pathways were screened by metabolomics and transcriptome analysis and correlation KEGG enrichment analysis , and the related network interaction diagram of differential metabolites and differentially expressed genes in key pathways was constructed and verified by RT⁃qPCR .
Results :Metabolomics analysis showed that 133 differential metabolites were screened from in the plain spleen control group (PSC group) and the plateau spleen test group (HST group) , 95 of which were up⁃regulated while 38 of which were down⁃regulated . KEGG enrichment analysis showed that they were mainly involved in NOD⁃like receptor signaling pathway , HIF⁃1 signaling pathway , cholesterol metabolism and other metabolic pathways . The results of transcriptome analysis showed that a total of 4213 differentially expressed genes were identified in PSC group and HST group , including 1947 up⁃regulated genes and 2266 down⁃regulated genes . KEGG was enriched in 173 signaling pathways , including NOD⁃like receptor signaling pathway , MAPK signaling pathway , NF⁃κB signaling pathway and other pathways . Comprehensive analysis showed that the differential metabolites and differentially expressed genes were obviously enriched in NOD⁃like receptor signaling pathway . Therefore , the correlation network interaction map was constructed for the differential metabolites ATP and differentially expressed genes in NOD⁃like receptor signaling pathway . RT⁃qPCR results showed that compared with PSC group , the expression levels of DEGs related to NOD1 and NOD2 (CHUK , TAB3 , MAPK8) in the signaling pathway of NOD⁃like receptor and NLRP1 ⁃CASP1 pathway (NLRP1b , CASP1) in HST group were significantly enhanced . The mRNA expression levels of downstream inflammatory factors IL⁃6 , IL⁃1 β , IL⁃18 , INF⁃γ and TNF⁃α were up⁃regulated and differentially expressed .
Conclusion : Based on the combined analysis of metabolomics and transcriptomics , it was found that hypoxia stimulation at high altitude may affect the NOD⁃like receptor signaling pathway in vivo , and the differential metabolite ATP is positively correlated with the differential key genes in the pathway . ATP mediates the release of downstream inflammatory factors by activating NOD1 , NOD2 pathways and NLRP1 inflammable⁃CASP1 pathways . Inflammatory response occurred in spleen tissue of mice.
- Full text:2024071618502038991高原低氧通过NOD样受体信...路诱导小鼠脾脏组织炎症反应_王嘉阳.pdf
