School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland.
J Steroid Biochem Mol Biol. 2019 Apr;188:71-76. doi: 10.1016/j.jsbmb.2018.11.019. Epub 2018 Dec 8.
In the vitamin D intervention study VitDbol (NCT02063334) blood samples were drawn directly before an oral bolus (2000 μg vitamin D) and 24 h later. The focus of phase II of VitDbol was the transcriptome-wide analysis of the effects of vitamin D gene expression in human peripheral blood mononuclear cells (PBMCs). All five participants responded in an individual fashion to the bolus by increases in serum levels of the vitamin D metabolites 25-hydroxyvitamin D (25(OH)D) and 1α,25-dihydroxyvitamin D (1,25(OH)D). RNA sequencing identified 15.040 commonly expressed genes in PBMCs, 702 (4,7%) of which were significantly (p < 0,05) affected by the vitamin D bolus. KEGG pathway analysis suggested that these genes are involved in general protein translation, monocyte differentiation and cellular growth control. Previously published transcriptome-wide studies in comparable cell systems confirmed 234 of the 702 vitamin D target genes, leaving many genes, such as HLA-A and HLA-C, as novel discoveries. Interestingly, in vivo stimulated PBMCs of this study showed a larger number of common vitamin D target genes with the monocytic cell line THP-1 than with in vitro stimulated PBMCs. The expression pattern of vitamin D target genes differed significantly between individuals and the average expression change can serve as a marker for vitamin D responsiveness. In conclusion, this study demonstrates that under in vivo conditions changes in 25(OH)D and 1,25(OH)D serum concentrations alter the expression of more than 700 vitamin D target genes in human leukocytes.
在维生素 D 干预研究 VitDbol（NCT02063334）中，直接在口服冲击（2000μg 维生素 D）前和 24 小时后采集血样。VitDbol 二期研究的重点是人类外周血单核细胞（PBMCs）中维生素 D 基因表达的转录组分析。所有五名参与者均以个体方式对冲击作出反应，表现为血清中维生素 D 代谢物 25-羟维生素 D（25（OH）D）和 1α，25-二羟维生素 D（1,25（OH）D）水平升高。RNA 测序鉴定了 PBMCs 中 15040 个共同表达的基因，其中 702 个（4.7%）基因受到维生素 D 冲击的显著影响（p<0.05）。KEGG 途径分析表明，这些基因参与一般蛋白质翻译、单核细胞分化和细胞生长控制。以前在类似细胞系统中进行的全转录组研究证实了 702 个维生素 D 靶基因中的 234 个，留下了许多基因，如 HLA-A 和 HLA-C，作为新的发现。有趣的是，与体外刺激的 PBMCs 相比，本研究中体内刺激的 PBMCs 显示出更多常见的维生素 D 靶基因，与单核细胞系 THP-1 相比。维生素 D 靶基因的表达模式在个体之间有显著差异，平均表达变化可作为维生素 D 反应性的标志物。总之，本研究表明，在体内条件下，25（OH）D 和 1,25（OH）D 血清浓度的变化改变了人类白细胞中超过 700 个维生素 D 靶基因的表达。
