A Transcriptomic Analysis of Physiological Significance of Hypoxia-inducible Factor-1α in Myogenesis and Carbohydrate Metabolism of Genioglossus in Mice

Abstract

Background: Chronic intermittent hypoxia is the most remarkable feature of obstructive sleep apnea/hypopnea syndrome and it can induce the change of hypoxia-inducible factor-1α (HIF-1α) expression and contractile properties in the genioglossus. To clarify the role of HIF-1α in contractile properties of the genioglossus, this study generated and compared high-throughput RNA-sequencing data from genioglossus between HIF-1α conditional knockout (KO) mice and littermate wild-type (WT) mice. Methods: KO mice were generated with cre-loxP strategy. Gene expression profile analysis was performed using gene enrichment analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differently expressed messenger RNAs were performed to identify the related pathways and biological functions. Six differentially expressed genes (DEGs) were validated by qualitative reverse transcription polymerase chain reaction. Results: A total of 142 (77 upregulated and 65 downregulated) transcripts were found to exhibit statistically significant difference between the HIF-1α-KO and WT mice. GO and KEGG analyses indicated that DEGs included genes involved in “skeletal muscle cell differentiation,” “muscle organ development,” “glucose metabolic process,” “glycogen biosynthetic and metabolic process,” etc. Conclusion: This study might provide evidence that HIF-1α affects the expression of multiple genes involved in the myogenesis, muscle development, and carbohydrate metabolism through transcriptome analysis in conditional HIF-1α-KO mice.

Keywords

• Carbohydrate Metabolism; Genioglossus; Hypoxia-inducible Factor-1α; Myogenesis; Transcriptomic Analysis