Transcriptomics ⁃based study of the mechanism of the effect of plateau hypoxia stress on energy metabolism⁃related pathways in the mouse kidney
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摘要:
目的：基于转录组测序技术研究小鼠肾脏组织在适应高原低氧胁迫过程中的基因表达和相应的分子机制。方法：在海拔4 200 m（高原肾脏实验组，high-altitude kidney test group，HKT）和海拔400 m（平原肾脏对照组，plain kidney control group， PKC）的环境下分别饲养C57BL/6小鼠，30 d后无菌取出小鼠肾脏组织用高通量测序技术（RNA-sequencing，RNA-Seq）进行转录组测序。将 HKT 组和 PKC 组的测序结果进行基因本体数据库（gene ontology，GO）注释分析和京都基因和基因组百科全书数据库（Kyoto encyclopedia of genes and genomes，KEGG）富集分析，并通过实时荧光定量 PCR（real-time quantitative PCR， RT-qPCR）实验验证测序结果的可靠性。结果：相比于PKC组，HKT组中1 349个基因表达上调（P < 0.05），1 658个基因表达下调 （P < 0.05）。其中催乳素受体（prolactin receptor，PRLR）、载脂蛋白E（apolipoprotein E，APOE）、载脂蛋白A4（apolipoprotein A4， APOA4）、细胞色素 C（cytochrome C somatic，CYCS）、酰基辅酶 A 氧化酶 2（acyl-coenzyme A oxidase 1，ACOX2）、细胞色素 C 氧化酶亚基5A（cytochrome C oxidase subunit 5A，COX5A）、细胞色素C氧化酶亚基5B（cytochrome C oxidase subunit 5B，COX5B）、 细胞色素C氧化酶亚基7A（cytochrome C oxidase subunit 7A，COX7A）和热休克蛋白β-1（heat shock protein β-1，HSPB1）等基因显著富集。GO注释分析和KEGG富集分析结果显示，差异基因显著富集在细胞器内膜、线粒体内膜和线粒体蛋白复合物等部位，此外过氧化物酶体、氧化磷酸化、产热、碳代谢以及三羧酸循环等通路显著富集。结论：高原低氧刺激可能通过影响机体的能量代谢相关通路致使机体氧化应激、炎症反应和脂质代谢失衡。
Abstract:
Objective：To investigate the molecular mechanisms of gene expression and response in mouse kidney tissue during adaptation to hypoxic stress in the plateau based on transcriptome sequencing technology. Methods：C57BL/6 mice were reared at 4 200 m(high altitude kidney test group，HKT)and 400 m(plain kidney control group，PKC)above sea level，and kidney tissues were removed aseptically after 30 days for transcriptome sequencing using high-throughput RNA-sequencing(RNA-Seq). The sequencing results from the HKT and PKC groups were analyzed by gene ontology(GO)annotation and enrichment in the Kyoto encyclopedia of genes and genomes(KEGG)，and the reliability of the sequencing results was verified by real -time quantitative PCR(RT-qPCR). Results：Compared to the PKC group，1 349 genes expression were upregulated(P ＜ 0.05)and 1 658 genes expression were downregulated in the HKT group(P ＜ 0.05). Among them，prolactin receptor(PRLR)，apolipoprotein E(APOE)，apolipoprotein A4 (APOA4)，cytochrome C somatic(CYCS)，acyl-coenzyme A oxidase 1(ACOX2)，cytochrome C oxidase subunit 5A(COX5A)， cytochrome C oxidase subunit 5B(COX5B)，cytochrome C oxidase subunit 7A(COX7)and heat shock protein β-1(HSPB1)genes were significantly enriched. GO annotation analysis and KEGG enrichment analysis showed that differential genes were significantly enriched in organelle inner membrane，mitochondrial inner membrane and mitochondrial protein complexes，in addition to peroxisomal，oxidative phosphorylation，thermogenesis，carbon metabolism and tricarboxylic acid cycle pathways. Conclusion：Hypoxic stimulation at high altitude may cause oxidative stress，inflammatory response and imbalance of lipid metabolism in the body by affecting energy metabolism-related pathways.
