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暴露于芥子气的皮肤、血清和肺样本中miR-21-5p、miR-20a-5p、转化生长因子-β1(TGF-β1)和转化生长因子-β受体2(TGF-β受体2)的差异表达

Differential Expression of miR-21-5p, miR-20a-5p, TGF-β1, and TGF-β Receptor 2 in Skin, Serum, and Lung Samples Exposed to Sulfur Mustard.

作者信息

Valizadeh Mohadeseh, Irani Shiva, Tavallaei Mahmood, Soleimani Masoud

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Genetics Research Center, Baqiatallah Medical Sciences University, Tehran, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2023 Sep 3;22(4):366-378. doi: 10.18502/ijaai.v22i4.13609.

Abstract

Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA (miR) transcript levels are found in pulmonary diseases and even inflammation. Therefore, we evaluated the expression levels of miR-20a-5p, miR-21-5p, and two target transcripts (transforming growth factor-beta [TGF-β1] and TGF-β receptor 2 [TGFR2]) in lung, serum, and skin samples from patients exposed to SM. Total RNA was extracted from lung, serum, and skin samples of patients with moderate (n=10) and high (n=10) SM exposure, as well as 10 healthy subjects. Following the synthesis of complementary deoxyribonucleic acid using real-time polymerase chain reaction, we determined the expression levels of miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 transcripts. Furthermore, we evaluated the sensitivity and specificity of the chosen miRs by employing receiver operating characteristic (ROC) curves and calculating the area under the ROC curve. The results showed that miR-20a-5p and miR-21-5p expressions in the groups with moderate and high SM exposure were significantly lower than the normal controls. The expression analysis demonstrated that TGFR2 was significantly less expressed in skin samples exposed to SM in both groups of patients compared with healthy controls. Furthermore, the TGF-β1 expression in the skin samples of the group with moderate SM exposure was lower than that of the normal control group. Our findings suggest that miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 expressions could be used as potential biomarkers for discriminating SM-exposed patients from healthy individuals.

摘要

硫芥(SM)或芥子气是一种糜烂性化学毒剂,可通过引发炎症和氧化损伤导致肺部损害。肺部疾病甚至炎症中都存在微小RNA(miR)转录水平的改变。因此,我们评估了暴露于硫芥的患者的肺、血清和皮肤样本中miR-20a-5p、miR-21-5p以及两个靶转录本(转化生长因子-β [TGF-β1]和TGF-β受体2 [TGFR2])的表达水平。从硫芥暴露程度为中度(n=10)和高度(n=10)的患者以及10名健康受试者的肺、血清和皮肤样本中提取总RNA。使用实时聚合酶链反应合成互补脱氧核糖核酸后,我们测定了miR-20a-5p、miR-21-5p、TGF-β1和TGFR2转录本的表达水平。此外,我们通过绘制受试者工作特征(ROC)曲线并计算ROC曲线下面积来评估所选miR的敏感性和特异性。结果显示,中度和高度硫芥暴露组中miR-20a-5p和miR-21-5p的表达明显低于正常对照组。表达分析表明,与健康对照组相比,两组患者中暴露于硫芥的皮肤样本中TGFR2的表达明显降低。此外,中度硫芥暴露组皮肤样本中TGF-β1的表达低于正常对照组。我们的研究结果表明,miR-20a-5p、miR-21-5p、TGF-β1和TGFR2的表达可作为区分硫芥暴露患者和健康个体的潜在生物标志物。

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