The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD.

The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD.
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小气道平滑肌中NOX4的表达与COPD病情严重程度相关

DOI:
10.1155/2016/2891810
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发表时间:
2016
影响因子:
--
通讯作者:
Chen J
Chen J
中科院分区:
生物学3区
文献类型:
--
作者:
Liu X;Hao B;Ma A;He J;Liu X;Chen J

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气道平滑肌(ASM)重构是慢性阻塞性肺疾病(COPD)的重要标志,而产生的NADPH氧化酶(NOxs)在COPD的发病机制中起着重要作用。本研究采用半定量的形态和/或免疫组织化学方法,研究了NOX4在慢性阻塞性肺疾病小气道间质中的表达及其与间质肥大/增生、临床肺功能及转化生长因子β(β)表达的关系。结果显示,慢性阻塞性肺疾病患者小气道间质中NOX4和转化生长因子-β的表达增加,并伴有间质肿块体积的增大。COPD患者ASM中NOX4蛋白的丰度随病情加重而增加,与肺功能呈负相关。此外,NOX4的表达与α-SMA共定位,并发现NOX4的表达增加伴随着转化生长因子-β在COPD小气道ASM的表达上调。这些结果表明,NOX4可能是小气道间质重塑的关键调节因子,部分是通过与转化生长因子-β信号相互作用在慢性阻塞性肺疾病发病机制中发挥作用的,值得进一步研究。
Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor β (TGF-β) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-β, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF-β in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF-β signaling in the pathogenesis of COPD, which warrants further investigation.
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