Integrating metabolomics and transcriptomics to investigate the effects of changes in renal adenosine 5'-monophosphate and arginine metabolism on the mTOR pathway under chronic hypoxia

<h4>Objectives</h4>Hypoxia leads to pathophysiological changes in the body. Kidneys are important organs essential for maintaining normal body function. The metabolic changes in renal under chronic hypoxia are still unclear. To investigate how chronic hypobaric hypoxia alters renal metabolites and mTOR-related signalling pathways in mouse kidney.<h4>Methods</h4>The tests used renal tissues from mice maintained for 4 weeks in hypoxia and normoxia at altitudes of 5000 m and 50 m. Mice renal at different altitudes were screened for differential metabolites and genes using non-targeted metabolomics and transcriptomics. The effect of hypoxia on renal tissue metabolic pathways was clarified using Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses.<h4>Results</h4>A total of 120 and 79 markedly altered metabolites were identified as differential metabolites in the positive and negative ion modes, respectively. A total of 4155 significantly altered genes were identified, of which 2342 were upregulated and 1813 downregulated in the high-altitude group.<h4>Conclusions</h4>A combined analysis of metabolomics and transcriptomics revealed that adenosine 5'-monophosphate(AMP) and arginine were associated with changes in the renal mTOR signalling pathway under conditions of chronic hypoxia. Our findings on AMP and arginine metabolism and differentially expressed genes(DEGs) provide insights into chronic hypoxia-induced mTOR changes in kidney.