Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension.
Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension.
复制标题
DOI：
10.1002/art.30159
复制
发表时间：
2011-03
影响因子：
--
通讯作者：
Feghali-Bostwick, Carol A.
中科院分区：
文献类型：
--
作者：
Hsu, Eileen;Shi, Haiwen;Jordan, Rick M.;Lyons-Weiler, James;Pilewski, Joseph M.;Feghali-Bostwick, Carol A.
系统性硬化症（SSc）的肺部并发症，包括肺纤维化（PF）和肺动脉高压（PAH），是死亡的主要原因。我们将 SSc 肺组织和匹配的原代肺成纤维细胞的分子指纹与正常供体、特发性肺纤维化 (IPF) 和特发性肺动脉高压 (IPAH) 患者的分子指纹进行了比较。肺组织取自 33 名接受肺移植的 SSc 患者。将来自主要患有 PF 或 PAH 的 SSc 患者亚组的组织和细胞与来自正常供体、患有 IPF 或 IPAH 的患者的组织和细胞进行比较。使用效率分析来分析微阵列数据以确定最佳数据处理方法。实时PCR和免疫组织化学分别用于确认mRNA和蛋白质的差异水平。我们确定了分别在肺和原代成纤维细胞中差异表达的 242 个和 335 个基因的共识。 SSc-PF 和 IPF 肺中丰富的功能群包括纤维化、胰岛素样生长因子信号传导和小窝蛋白介导的内吞作用。 SSc-PAH 和 IPAH 肺共有的功能组包括抗原呈递、趋化因子活性和 IL-17 信号传导。通过对仔细表型的 SSc 和对照肺组织进行微阵列分析，我们证明了与特发性肺病相比，SSc 相关肺病患者的组织和成纤维细胞具有不同的分子特征。生成了疾病（SSc）和表型（PF 与 PAH）特异性的独特分子特征。这些特征为 SSc 肺病的发病机制和潜在治疗靶点提供了新的见解。
Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease.
登录
查看更多内容
影响因子：
6
作者：
Pilewski, JM;Liu, LX;Feghali-Bostwick, CA
通讯作者：
Feghali-Bostwick, CA
硬皮病皮肤的基因表达特征中的分子亚群。
影响因子：
3.7
作者：
Milano A;Pendergrass SA;Sargent JL;George LK;McCalmont TH;Connolly MK;Whitfield ML
通讯作者：
Whitfield ML
影响因子：
7.8
作者：
Grigoryev, Dmitry N.;Mathai, Stephen C.;Hassoun, Paul M.
通讯作者：
Hassoun, Paul M.
影响因子：
4.8
作者：
Amaar, YG;Thompson, GR;Mohan, S
通讯作者：
Mohan, S
DOI：
10.1164/rccm.2106012
发表时间：
2002-06-15
影响因子：
24.7
作者：
Bouros, D;Wells, AU;du Bois, RM
通讯作者：
du Bois, RM