Pathway analysis of transcriptomic data shows immunometabolic effects of vitamin D
Pathway analysis of transcriptomic data shows immunometabolic effects of vitamin D
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DOI：
10.1530/jme-17-0186
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发表时间：
2018-02-01
影响因子：
3.5
通讯作者：
Coort, Susan L.
中科院分区：
文献类型：
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作者：
Garcia, Amadeo Munoz;Kutmon, Martina;Coort, Susan L.
无偏基因组筛选分析突出了维生素D活性形式1，25-二羟基维生素D（1，25（OH）（2）D）的新免疫调节特性。然而，对所得基因表达数据的更清晰解释受到细胞模型特异性的限制。本研究的目的是通过系统地重新查询来自多个相关单核细胞模型（THP-1单核细胞系（THP-1）、单核细胞衍生的树突状细胞（DC）和单核细胞）的现有基因表达数据库，为与1，25（OH）（2）D先天免疫应答相关的常见基因调控途径提供更广泛的视角。维生素D受体（VDR）表达在多种免疫细胞类型中是常见的，因此，使用来自多种相关模型的数据进行基因表达的途径分析，为维生素D的免疫调节影响提供了一个全面的视角。一个生物信息学的工作流程，结合使用Pathway和WikiPathways的途径分析被用来比较每一组基因表达数据的基础上的途径水平的背景。使用这种策略，与TCA循环，氧化磷酸化和ATP合成和代谢相关的途径显示出在每个储存库模型中受到1，25（OH）（2）D的显著调节（Z分数3.52-8.22）。1，25（OH）（2）D对细胞凋亡相关通路和细胞凋亡调节也有共同的调节作用（Z-评分2.49-3.81）。与原代培养DC和单核细胞模型相反，THP-1骨髓单核细胞系显示出对与细胞增殖和DNA复制相关的途径的强烈调节（Z-评分6.1-12.6）。简而言之，本文提供的数据支持活性1，25（OH）（2）D作为免疫代谢的关键调节剂的基本作用。
Unbiased genomic screening analyses have highlighted novel immunomodulatory properties of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D). However, clearer interpretation of the resulting gene expression data is limited by cell model specificity. The aim of the current study was to provide a broader perspective on common gene regulatory pathways associated with innate immune responses to 1,25(OH)(2)D, through systematic re-interrogation of existing gene expression databases from multiple related monocyte models (the THP-1 monocytic cell line (THP-1), monocyte-derived dendritic cells (DCs) and monocytes). Vitamin D receptor (VDR) expression is common to multiple immune cell types, and thus, pathway analysis of gene expression using data from multiple related models provides an inclusive perspective on the immunomodulatory impact of vitamin D. A bioinformatic workflow incorporating pathway analysis using PathVisio and WikiPathways was utilized to compare each set of gene expression data based on pathway-level context. Using this strategy, pathways related to the TCA cycle, oxidative phosphorylation and ATP synthesis and metabolism were shown to be significantly regulated by 1,25(OH)(2)D in each of the repository models (Z-scores 3.52-8.22). Common regulation by 1,25(OH)(2)D was also observed for pathways associated with apoptosis and the regulation of apoptosis (Z-scores 2.49-3.81). In contrast to the primary culture DC and monocyte models, the THP-1 myelomonocytic cell line showed strong regulation of pathways associated with cell proliferation and DNA replication (Z-scores 6.1-12.6). In short, data presented here support a fundamental role for active 1,25(OH)(2)D as a pivotal regulator of immunometabolism.