mRNA expression profiling and pathway analysis of chronic intermittent hypoxia-induced pancreatic injury in ob/ob mice

ob/ob小鼠慢性间歇性缺氧诱导胰腺损伤的mRNA表达谱和通路分析

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Abstract

BACKGROUND: Increasing evidence suggests that messenger RNA (mRNA) is centrally involved in the initiation and progression of various diseases. However, its involvement in pancreatic injury resulting from obstructive sleep apnea (OSA) continues to be incompletely elucidated. The present investigation aimed to characterize mRNA expression changes using a murine model of chronic intermittent hypoxia (CIH) to provide new insights into the mechanisms underlying OSA-associated pancreatic injury. METHODS: An ob/ob murine model for pancreatic injury triggered by CIH was established. RNA sequencing (RNA-seq) was conducted to detect differentially expressed mRNAs, and subsequently Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to delineate the associated functional annotations and signaling cascades. Furthermore, several selected mRNAs were validated using reverse transcription PCR (RT-qPCR). Finally, we constructed a protein-protein interaction (PPI) network to delineate the interplay among the protein targets of the differentially expressed genes (DEGs). RESULTS: In a mouse model of CIH-induced pancreatic dysfunction, 481 mRNAs were upregulated and 165 were downregulated. KEGG enrichment analysis indicated that the NOD-like receptor signaling pathway is implicated in CIH-induced pancreatic dysfunction. Subsequently, several differentially expressed mRNAs were subjected to RT-qPCR validation. On the basis of these data, a subset of DEGs were selected to construct a PPI network. CONCLUSION: Overall, we identified 646 DEGs in the CIH mouse model. These results may offer important perspectives on the pathophysiological processes that underlie OSA-induced diabetes mellitus.

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