Piotrowski W J, Kiszałkiewicz J, Pastuszak-Lewandoska D, Antczak A, Górski P, Migdalska-Sęk M, Górski W, Czarnecka K, Nawrot E, Domańska D, Brzeziańska-Lasota E
Department of Pneumology and Allergy, First Chair of Internal Diseases, Medical University of Lodz, 251 Pomorska St., 92-213, Lodz, Poland.
Adv Exp Med Biol. 2015;852:59-69. doi: 10.1007/5584_2014_106.
Lung fibrosis is a complication of sarcoidosis, in which TGF-β/Smad pathway may play an important role. We evaluated gene expression of TGF-β1, SMAD2, 3 and 7 in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes of sarcoidosis patients (n=94) to better understand the mechanisms of sarcoid inflammation. The relative gene expression was analyzed by qPCR method. Selected clinical/radiological features and biochemical markers were taken into account in the analysis. We found that TGF-β1 and SMAD3 expressions in PB lymphocytes were significantly higher in sarcoidosis patients. Up-regulation of SMAD7 (inhibitory Smad) and down-regulation of SMAD3 in BAL cells in all subgroups were found. The expression of TGF-β1 in PB lymphocytes was the highest in patients with lung parenchymal involvement and in the insidious onset phenotype. The expression of TGF-β1 in BAL cells was higher in patients with abnormal spirometry (p=0.012), and TGF-β1 and SMAD3 in patients with restrictive pattern (p=0.034 and 0.031, respectively). Several statistically significant negative correlations were found between the expression levels of SMAD2 and 3 in BAL cells and various LFT parameters. We conclude that TGF-β/Smad pathway is involved in the pathogenesis of pulmonary sarcoidosis. These biomarkers (especially TGF-β1, SMAD2 and 3) are of a negative prognostic value.
肺纤维化是结节病的一种并发症，其中转化生长因子-β/信号转导和转录激活因子（TGF-β/Smad）通路可能起重要作用。我们评估了结节病患者（n = 94）支气管肺泡灌洗（BAL）细胞和外周血（PB）淋巴细胞中TGF-β1、SMAD2、3和7的基因表达，以更好地了解结节病炎症的机制。通过定量聚合酶链反应（qPCR）方法分析相对基因表达。分析中考虑了选定的临床/放射学特征和生化标志物。我们发现结节病患者PB淋巴细胞中TGF-β1和SMAD3的表达显著更高。在所有亚组的BAL细胞中均发现SMAD7（抑制性Smad）上调和SMAD3下调。PB淋巴细胞中TGF-β1的表达在有肺实质受累的患者和隐匿起病表型患者中最高。肺活量测定异常的患者BAL细胞中TGF-β1的表达更高（p = 0.012），限制性模式患者中TGF-β1和SMAD3的表达更高（分别为p = 0.034和0.031）。在BAL细胞中SMAD2和3的表达水平与各种肝功能参数之间发现了几个具有统计学意义的负相关。我们得出结论，TGF-β/Smad通路参与了肺结节病的发病机制。这些生物标志物（尤其是TGF-β1、SMAD2和3）具有负面预后价值。
