Liu Xianyan, Hao Binwei, Ma Ailing, He Jinxi, Liu Xiaoming, Chen Juan
Department of Pulmonary and Critical Care Medicine, The General Hospital of Ningxia Medical University, Yinchuan 750004, China; Ningxia Medical University, Yinchuan 750004, China; Binzhou People's Hospital, Binzhou, Shandong 256600, China.
Department of Pulmonary and Critical Care Medicine, The General Hospital of Ningxia Medical University, Yinchuan 750004, China; Ningxia Medical University, Yinchuan 750004, China.
Biomed Res Int. 2016;2016:2891810. doi: 10.1155/2016/2891810. Epub 2016 Aug 30.
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 (TGF-) 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-, 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 -SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF- 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- signaling in the pathogenesis of COPD, which warrants further investigation.
气道平滑肌（ASM）重塑是慢性阻塞性肺疾病（COPD）的一个标志，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOXs）产生的活性氧（ROS）在COPD发病机制中起关键作用。在本研究中，通过半定量形态学和/或免疫组织化学染色方法，研究了COPD小气道ASM中NOX4的表达及其与ASM肥大/增生、临床肺功能以及转化生长因子（TGF-）表达的相关性。结果显示，在COPD患者的小气道ASM中发现NOX4和TGF-表达升高，同时ASM质量增加。COPD患者ASM中NOX4蛋白的丰度随疾病严重程度增加，且与肺功能呈负相关。此外，NOX4和ASM标志物α-SMA的表达共定位，并且在COPD肺小气道的ASM中发现NOX4表达增加伴随着TGF-表达上调。这些结果表明，NOX4可能是小气道ASM重塑的关键调节因子，部分是通过在COPD发病机制中与TGF-信号相互作用的机制，这值得进一步研究。
