miR-155 in the progression of lung fibrosis in systemic sclerosis.
miR-155 in the progression of lung fibrosis in systemic sclerosis.
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DOI：
10.1186/s13075-016-1054-6
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发表时间：
2016-07-05
影响因子：
4.9
通讯作者：
Lafyatis R
中科院分区：
文献类型：
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作者：
Christmann RB;Wooten A;Sampaio-Barros P;Borges CL;Carvalho CR;Kairalla RA;Feghali-Bostwick C;Ziemek J;Mei Y;Goummih S;Tan J;Alvarez D;Kass DJ;Rojas M;de Mattos TL;Parra E;Stifano G;Capelozzi VL;Simms RW;Lafyatis R
MicroRNA (miRNA) 控制 mRNA 稳定性的关键要素，并可能导致系统性硬化症相关间质性肺疾病 (SSc-ILD) 中观察到的肺基因表达失调。我们分析了 SSc-ILD 患者组织和细胞的 miRNA 基因表达。使用慢性肺纤维化小鼠模型。从 12 名 SSc-ILD 患者和 5 名对照者的肺组织中分离出 RNA。在基线和治疗后 2-3 年进行高分辨率计算机断层扫描 (HRCT)。从健康对照和 SSc-ILD 患者中分离出肺成纤维细胞和外周血单核细胞 (PBMC)。通过微阵列、定量聚合酶链式反应和/或 Nanostring 分析 miRNA 和 mRNA；通过DNA智能分析(DIANA)-miRPath v2.0软件进行通路分析。将野生型和 miR-155 缺陷型 (miR-155ko) 小鼠暴露于博莱霉素。肺部 miRNA 微阵列数据通过 185 个差异表达的 miRNA (q<<0.25) 将 SSc-ILD 患者与健康对照区分开来。 DIANA-miRPath 揭示了与最失调的 miRNA 相关的 57 条京都基因和基因组百科全书通路。 miR-155 和 miR-143 与 HRCT 评分的进展密切相关。几次刺激后，肺成纤维细胞仅轻度表达 miR-155/miR-21。 SSc-ILD 中 miR-155 PBMC 表达与肺功能测试密切相关。与野生型小鼠相比，miR-155ko 小鼠在博来霉素暴露后出现更轻微的肺纤维化，存活时间更长，并且几个基因的肺诱导更弱。 SSc-ILD 患者的肺部和 PBMC 中的 miRNA 失调。基于 mRNA-miRNA 相互作用分析和通路工具，miRNA 可能在疾病的进展中发挥作用。我们的研究结果表明，靶向 miR-155 可能为 SSc-ILD 提供一种新的治疗策略。本文的在线版本 (doi:10.1186/s13075-016-1054-6) 包含补充材料，可供授权用户使用。
MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2–3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. The online version of this article (doi:10.1186/s13075-016-1054-6) contains supplementary material, which is available to authorized users.