Expression profile of mitochondrial voltage-dependent anion channel-1 (VDAC1) influenced genes is associated with pulmonary hypertension.
Expression profile of mitochondrial voltage-dependent anion channel-1 (VDAC1) influenced genes is associated with pulmonary hypertension.
复制标题
DOI：
10.4196/kjpp.2017.21.3.353
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Ko JH
中科院分区：
文献类型：
--
作者：
Zhou T;Tang H;Han Y;Fraidenburg D;Kim YW;Lee D;Choi J;Bang H;Ko JH
由于线粒体电压依赖性阴离子通道-1(VDAC1)在钙离子转运和细胞凋亡中的作用，许多人类疾病都与其有关。最近的研究表明，VDAC1可能与内皮依赖性一氧化氮合酶(ENOS)相互作用。VDAC1表达降低可能限制VDAC1和eNOS之间的物理相互作用，从而损害一氧化氮的产生，导致心血管疾病，包括肺动脉高压(PAH)。在这份报告中，我们进行了全基因组表达数据的荟萃分析，以确定与PAH病理生物学相关的VDAC1影响基因。首先，我们鉴定了野生型和Vdac1基因敲除的小鼠胚胎成纤维细胞在低氧条件下的差异表达基因。这些基因被认为是受VDAC1缺乏的影响。基因本体论分析表明，受VDAC1影响的基因与PAH的病理生物学密切相关。其次，从受VDAC1影响的基因中提取出一个分子特征。我们认为，VDAC1在PAH中具有保护作用，VDAC1影响基因的基因表达特征可用于1)预测肺部疾病继发肺动脉高压的严重程度，2)鉴别特发性肺动脉高压患者和对照组，3)鉴别特发性肺动脉高压与结缔组织病相关的PAH。
Several human diseases have been associated with mitochondrial voltage-dependent anion channel-1 (VDAC1) due to its role in calcium ion transportation and apoptosis. Recent studies suggest that VDAC1 may interact with endothelium-dependent nitric oxide synthase (eNOS). Decreased VDAC1 expression may limit the physical interaction between VDAC1 and eNOS and thus impair nitric oxide production, leading to cardiovascular diseases, including pulmonary arterial hypertension (PAH). In this report, we conducted meta-analysis of genome-wide expression data to identify VDAC1 influenced genes implicated in PAH pathobiology. First, we identified the genes differentially expressed between wild-type and Vdac1 knockout mouse embryonic fibroblasts in hypoxic conditions. These genes were deemed to be influenced by VDAC1 deficiency. Gene ontology analysis indicates that the VDAC1 influenced genes are significantly associated with PAH pathobiology. Second, a molecular signature derived from the VDAC1 influenced genes was developed. We suggest that, VDAC1 has a protective role in PAH and the gene expression signature of VDAC1 influenced genes can be used to i) predict severity of pulmonary hypertension secondary to pulmonary diseases, ii) differentiate idiopathic pulmonary artery hypertension (IPAH) patients from controls, and iii) differentiate IPAH from connective tissue disease associated PAH.