Expression of Let-7 family microRNAs in skin correlates negatively with severity of pulmonary hypertension in patients with systemic scleroderma.
Expression of Let-7 family microRNAs in skin correlates negatively with severity of pulmonary hypertension in patients with systemic scleroderma.
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DOI：
10.1016/j.ijcha.2015.06.006
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发表时间：
2015-09-01
期刊：
影响因子：
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通讯作者：
Ogawa H
中科院分区：
文献类型：
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作者：
Izumiya Y;Jinnn M;Kimura Y;Wang Z;Onoue Y;Hanatani S;Araki S;Ihn H;Ogawa H
肺动脉高压（PH）是系统性硬皮病（SSc）患者的严重并发症，因此确定可以预测PH的存在和进展的因素非常重要。SSc患者进行皮肤活检以检查疾病的类型和严重程度。microRNA（miRNAs）是包括PH在内的多种心血管疾病的潜在生物标志物。我们测定了15例患有PH（n = 6）和没有PH（n = 9）的SSc患者的皮肤miRNA表达谱。制备来自PH和非PH患者的等量miRNA的混合物并用于miRNA PCR阵列分析。该分析在PH组中鉴定了591个上调的miRNA和57个下调的miRNA。其中，仅对Ct值小于35的miRNA进行进一步分析。当1.5倍的差异被认为是有意义的时，PH组中有32个miRNA上调，14个miRNA下调。有趣的是，14个下调的miRNAs中有5个属于let-7家族。结果通过使用每个miRNA的特异性引物的定量实时PCR进行验证，与9个非PH皮肤样品相比，6个PH中的5个let-7家族成员（let-7a，-7d，-7e，-7f，-7g）显著下调。let-7d和7b的表达水平与超声心动图测量的肺动脉压呈负相关。结果表明，皮肤miRNA是SSc患者PH存在和严重程度的潜在有用标志物。
Pulmonary hypertension (PH) is a serious complication in patients with systemic scleroderma (SSc), therefore it is important to identify the factors that could predict the presence and progression of PH. Skin biopsy is performed in patients with SSc to examine the type and severity of the disease. MicroRNAs (miRNAs) are potential biomarkers for various cardiovascular diseases including PH. We determined the skin miRNA expression profile in 15 SSc patients with (n = 6) and without PH (n = 9). A mixture of equal amounts of miRNAs from PH and non-PH patients were prepared and used for miRNA PCR array analysis. The analysis identified 591 upregulated miRNAs and 57 downregulated miRNAs in the PH group. Of these, only miRNAs with a Ct value of less than 35 were subjected to further analysis. When a 1.5-fold difference was considered meaningful, 32 miRNAs were upregulated and 14 miRNAs were downregulated in the PH group. Interestingly, 5 out of 14 downregulated miRNAs belonged to the let-7 family. The results were validated by quantitative real-time PCR with specific primer for each miRNA, which showed significant downregulation of five let-7 family members (let-7a, -7d, -7e, -7f, -7g) in 6 PH compared with 9 non-PH skin samples. The expression levels of let-7d and 7b correlated negatively with pulmonary arterial pressure measured by echocardiography. The results suggest that skin miRNA is a potentially useful marker for the presence and severity of PH in patients with SSc.