Hao Tong, Liu Yue-Hua, Li Yuan-Yuan, Lu Yun, Xu Hong-Yi
Department of Orthodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
Department of Orthodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072; Department of Orthodontics, Shanghai Stomatological Hospital, Shanghai 200001, China.
Chin Med J (Engl). 2017 Jul 5;130(13):1570-1577. doi: 10.4103/0366-6999.208235.
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.
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.
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.
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.
慢性间歇性缺氧是阻塞性睡眠呼吸暂停低通气综合征最显著的特征，它可诱导舌肌中缺氧诱导因子-1α（HIF-1α）表达及收缩特性的改变。为阐明HIF-1α在舌肌收缩特性中的作用，本研究生成并比较了HIF-1α条件性敲除（KO）小鼠和同窝野生型（WT）小鼠舌肌的高通量RNA测序数据。
采用cre-loxP策略构建KO小鼠。使用基因富集分析进行基因表达谱分析。对差异表达的信使RNA进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，以鉴定相关通路和生物学功能。通过定性逆转录聚合酶链反应验证6个差异表达基因（DEG）。
共发现142个转录本（77个上调和65个下调）在HIF-1α-KO小鼠和WT小鼠之间存在统计学显著差异。GO和KEGG分析表明，DEG包括参与“骨骼肌细胞分化”“肌肉器官发育”“葡萄糖代谢过程”“糖原生物合成和代谢过程”等的基因。
本研究可能通过对条件性HIF-1α-KO小鼠的转录组分析，提供证据表明HIF-1α影响参与肌生成、肌肉发育和碳水化合物代谢的多个基因的表达。
