Mami Somaye, Ghaffarpour Sara, Faghihzadeh Soghrat, Ghazanfari Tooba
Department of Immunology, Shahed University, Tehran, Iran.
Immunoregulation Research Center, Shahed University, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2019 Oct 23;18(5):473-478. doi: 10.18502/ijaai.v18i5.1895.
Sulfur mustard (SM) exposure injures different organs such as the lungs and leads to short and long term complications Transforming growth factor beta (TGF-β) has the main role in altering fibroblast activities linked to airways remodeling. Latency TGF beta binding proteins 1 (LTBP1 facilitates localization of TGF-β in the extracellular matrix. Mothers against decapentaplegic homolog 6 (Smad6) negatively regulates TGF-β signaling, thus establishing a main negative feedback loop. In this study, we investigated the expression of LTBP1 and Smad6 in the lung tissues of SM-exposed and control individuals. Lung formalin-fixed paraffin-embedded (FFPE) blocks of SM-exposed (20 samples) and control groups (20 samples) were collected from archival pathology department of several general hospitals. The total mRNA of lung FFPE tissues was extracted. Quality of the extracted mRNA was evaluated by an Agilent Bio analyzer and RNA was quantified using a Nano Drop. LTBP1 and Smad6 expression levels were evaluated by real-time PCR. LTBP1 expression levels did not change between the two groups (p=0.626), howeverSmad6 expression levels were significantly higher (2.6 fold) in SM-exposed individuals compared to the control group (p=0.001). Our results revealed that Smad6 may be involved in lung tissue remodeling process in SM-exposed patients. Smad6 regulates fibrotic alterations in lung tissue and its function as negative feedback mechanisms in TGF-β.
接触硫芥(SM)会损伤肺部等不同器官,并导致短期和长期并发症。转化生长因子β(TGF-β)在改变与气道重塑相关的成纤维细胞活性方面起主要作用。潜伏性TGF-β结合蛋白1(LTBP1)促进TGF-β在细胞外基质中的定位。抗五体不全同源蛋白6(Smad6)负向调节TGF-β信号传导,从而建立一个主要的负反馈回路。在本研究中,我们调查了接触SM者和对照组个体肺组织中LTBP1和Smad6的表达。从几家综合医院的档案病理科收集了接触SM者(20个样本)和对照组(20个样本)的肺福尔马林固定石蜡包埋(FFPE)组织块。提取肺FFPE组织的总mRNA。用安捷伦生物分析仪评估提取的mRNA质量,并用纳滴仪对RNA进行定量。通过实时PCR评估LTBP1和Smad6的表达水平。两组之间LTBP1表达水平没有变化(p=0.626),然而,与对照组相比,接触SM者的Smad6表达水平显著更高(2.6倍)(p=0.001)。我们的结果显示,Smad6可能参与接触SM患者的肺组织重塑过程。Smad6调节肺组织中的纤维化改变及其作为TGF-β负反馈机制的功能。