摘要Background:Cold exposure is linked to numerous diseases,yet the changes in key genes and pathways in mice under cold exposure remain unexplored.Understanding these alterations could offer insights into the mechanisms of cold resistance and contribute valuable ideas for treating cold-related diseases.Methods:The dataset GSE148361 was obtained from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified using the"limma"package in R software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on DEGs.The STRING(Search Tool for the Retrieval of Interacting Genes)database was used to construct a protein-protein interaction(PPI)network.Additionally,gene set enrichment analysis(GSEA)was conducted to identify pathways associated with key genes.miRNAs and upstream transcription factors(TFs)were predicted using the miRNet database.Results:A total of 208 DEGs were identified,with 137 upregulated and 71 downregulated.In biological processes,DEGs were enriched in nucleotide and purine-containing compound metabolism.For cellular components,DEGs were involved in condensed chromosomes and mitochondrial protein complexes.In molecular functions,proton transmembrane transporter activity was enriched.KEGG pathway analysis showed significant enrichment in biosynthesis of unsaturated fatty acids,fatty acids,and pyruvate metabolism.From the PPI network,12 hub genes were identified using MCODE.Four hub genes(Col3a1,Ifi203,Rtp4,Vcan)demonstrated similar trends in a validation set(GSE110420)and were significantly differentially expressed.GSEA analysis indicated that these four genes were enriched in pathways such as ECM-receptor interaction and cytokine-cytokine receptor interaction.The hub gene network included 93 miRNAs and one TF.Conclusion:This study identified four hub genes as potential diagnostic biomarkers for cold exposure,providing insights for further research on the effects of cold on gene expression and disease.