Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension
Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension
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DOI：
10.1152/ajpheart.00254.2009
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发表时间：
2010-04-01
影响因子：
4.8
通讯作者：
Ahmad, Ferhaan
中科院分区：
文献类型：
--
作者：
Rajkumar, Revathi;Konishi, Kazuhisa;Ahmad, Ferhaan
Rajkumar R, Konishi K, Richards TJ, Ishizawar DC, Wiechert AC, Kaminski N, Ahmad F.特发性肺动脉高压和继发性肺动脉高压的全基因组RNA表达谱分析。[J] .中国生物医学工程学报，2016,31(2):444 - 444。首次发表于2010年1月15日；doi: 10.1152 / ajpheart.00254.2009。特发性肺动脉高压（PAH）是一种以肺动脉重塑为特征的危及生命的疾病。本研究旨在确定与PAH发病机制相关的基因，而不是其他形式的肺动脉高压（PH）。使用全基因组微阵列分析，我们生成了迄今为止最大的肺组织样本RNA表达谱数据集，这些样本来自1)18名PAH受试者，2)8名PH继发于特发性肺纤维化（IPF）的受试者和3)13名正常受试者。在这三个队列中有4,734个基因的分子标记。我们发现了可能导致PAH发病的重要生物学变化，包括肌动蛋白运动、蛋白泛素化、cAMP、转化生长因子β、MAPK、雌激素受体、一氧化氮和PDGF信号的调节。骨形态发生蛋白受体II型表达下调，即使在没有该基因突变的受试者中也是如此。患有PAH的女性雌激素受体1的表达水平高于正常女性。实时定量PCR证实了PAH与正常对照和IPF继发PH之间存在以下基因的差异表达：具有血小板反应蛋白1型基序9的崩解素样和金属蛋白酶、与L1CAM同源的细胞粘附分子、细胞色素b（558）和β多肽、凝血因子II受体样3、a- myb成髓细胞病病毒致癌基因同源1、核受体辅助激活因子2、嘌呤能受体P2Y、血小板因子4、磷蛋白和原调节蛋白3。本研究表明继发于IPF的PAH和PH具有不同的基因表达特征，暗示了不同的病理生理机制。
Rajkumar R, Konishi K, Richards TJ, Ishizawar DC, Wiechert AC, Kaminski N, Ahmad F. Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension. Am J Physiol Heart Circ Physiol 298: H1235-H1248, 2010. First published January 15, 2010; doi: 10.1152/ajpheart.00254.2009.-Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by pulmonary arteriolar remodeling. This investigation aimed to identify genes involved specifically in the pathogenesis of PAH and not other forms of pulmonary hypertension (PH). Using genomewide microarray analysis, we generated the largest data set to date of RNA expression profiles from lung tissue specimens from 1) 18 PAH subjects and 2) 8 subjects with PH secondary to idiopathic pulmonary fibrosis (IPF) and 3) 13 normal subjects. A molecular signature of 4,734 genes discriminated among these three cohorts. We identified significant novel biological changes that were likely to contribute to the pathogenesis of PAH, including regulation of actin-based motility, protein ubiquitination, and cAMP, transforming growth factor-beta, MAPK, estrogen receptor, nitric oxide, and PDGF signaling. Bone morphogenic protein receptor type II expression was downregulated, even in subjects without a mutation in this gene. Women with PAH had higher expression levels of estrogen receptor 1 than normal women. Real-time quantitative PCR confirmed differential expression of the following genes in PAH relative to both normal controls and PH secondary to IPF: a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9, cell adhesion molecule with homology to L1CAM, cytochrome b(558) and beta-polypeptide, coagulation factor II receptor-like 3, A-myb myeloblastosis viral oncogene homolog 1, nuclear receptor coactivator 2, purinergic receptor P2Y, platelet factor 4, phospholamban, and tropomodulin 3. This study shows that PAH and PH secondary to IPF are characterized by distinct gene expression signatures, implying distinct pathophysiological mechanisms.