Altered epigenetic features in circulating nucleosomes in idiopathic pulmonary fibrosis.
Altered epigenetic features in circulating nucleosomes in idiopathic pulmonary fibrosis.
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DOI：
10.1186/s13148-017-0383-x
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发表时间：
2017
影响因子：
5.7
通讯作者：
Louis R
中科院分区：
文献类型：
--
作者：
Guiot J;Struman I;Chavez V;Henket M;Herzog M;Scoubeau K;Hardat N;Bondue B;Corhay JL;Moermans C;Louis R
特发性肺纤维化（IPF）是一种原因不明的进行性、致死性肺部疾病，具有高度可变和不可预测的临床病程。多态性和环境诱导的表观遗传变异似乎决定了个体对肺纤维化发展的易感性。我们研究了50例IPF患者无细胞核小体（cf核小体）上的循环表位。我们比较了未经治疗的IPF（n = 23）与接受抗纤维化治疗的IPF（n = 27）和健康受试者（HS）（n = 27）。我们分析了五种cf核小体的血清水平，包括结合的HMGB1（加合到高迁移率生长蛋白B1上的核小体）、mH2A1.1（含有组蛋白变体mH2A1.1的核小体）、5mC（与甲基化DNA相关的核小体）以及H3K9Ac和H3K27Ac（与组蛋白H3在赖氨酸9或27残基处乙酰化相关的核小体）。我们的研究结果显示，IPF患者血清中结合的HMGB1、mH2A1.1、5mC、H3K9Ac和H3K27Ac水平显著低于HS患者（分别为p < 0.001、p <0.001、p < 0.001和p < 0.0001）。此外，我们发现未经治疗的IPF患者与接受抗纤维化治疗的患者之间的表观遗传谱差异，未经治疗的患者的mH2A1.1和5mC显著低于经治疗的患者（分别为p < 0.01和p < 0.05）。四种cf核小体（HMGB1、5mC、H3K9Ac和H3K27Ac）的组合允许以良好的决定系数（R2 = 0.681）区分IPF与HS。通过该逻辑回归计算的ROC曲线的AUC为0.93（p < 0.001），其中91%的灵敏度和80%的特异性。我们的观察表明cf核小体（结合HMGB1、mH2A1.1、5mC、H3K9Ac和H3K27Ac）可能具有作为诊断和治疗反应的生物标志物的潜力。这些结果值得在纵向队列中进一步验证。
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disorder of unknown origin with a highly variable and unpredictable clinical course. Polymorphisms and environmentally induced epigenetic variations seem to determine individual susceptibility to the development of lung fibrosis. We have studied circulating epitopes on cell-free nucleosomes (cfnucleosomes) in 50 IPF patients. We have compared untreated IPF (n = 23) with IPF receiving antifibrotic therapy (n = 27) and healthy subjects (HS) (n = 27). We analyzed serum levels of five cfnucleosomes including bound HMGB1 (nucleosomes adducted to high-mobility growth protein B1), mH2A1.1 (nucleosomes containing the histone variant mH2A1.1), 5mC (nucleosomes associated with methylated DNA), and H3K9Ac and H3K27Ac (nucleosomes associated with histone H3 acetylated at lysine 9 or 27 residue). Our findings showed that serum levels of bound HMGB1, mH2A1.1, 5mC, H3K9Ac, and H3K27Ac were significantly lower in IPF patients than in HS (p < 0.001, p < 0.001, p < 0.01, p < 0.001, and p < 0.0001, respectively). Moreover, we found differences in epigenetic profiles between untreated IPF patients and those receiving anti-fibrotic therapy with mH2A1.1 and 5mC being significantly lower in untreated than in treated patients (p < 0.01 and p < 0.05, respectively). Combination of four cfnucleosomes (HMGB1, 5mC, H3K9Ac, and H3K27Ac) allow to discriminate IPF vs HS with a good coefficient of determination (R 2 = 0.681). The AUC for the ROC curve computed by this logistic regression was 0.93 (p < 0.001) with 91% sensitivity at 80% specificity. Our observations showed that cfnucleosomes (bound HMGB1, mH2A1.1, 5mC, H3K9Ac, and H3K27Ac) might have potential as biomarkers for diagnosis and treatment response. These results deserve further validation in longitudinal cohorts.
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影响因子：
29.4
作者：
Kang R;Zhang Q;Hou W;Yan Z;Chen R;Bonaroti J;Bansal P;Billiar TR;Tsung A;Wang Q;Bartlett DL;Whitcomb DC;Chang EB;Zhu X;Wang H;Lu B;Tracey KJ;Cao L;Fan XG;Lotze MT;Zeh HJ 3rd;Tang D
通讯作者：
Tang D
DOI：
10.1165/rcmb.2007-0330oc
发表时间：
2008-10-01
影响因子：
6.4
作者：
Hamada, Naoki;Maeyama, Takashige;Nakanishi, Yoichi
通讯作者：
Nakanishi, Yoichi
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
4.3
作者：
Kropski JA;Lawson WE;Young LR;Blackwell TS
通讯作者：
Blackwell TS
特发性肺纤维化的表观遗传学。
DOI：
10.1016/j.trsl.2014.03.011
发表时间：
2015-01
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Yang IV;Schwartz DA
通讯作者：
Schwartz DA