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人钙激活氯离子通道1基因表达增加与中国哮喘患者气道黏液过度分泌相关。

Increased expression of human calcium-activated chloride channel 1 gene is correlated with mucus overproduction in Chinese asthmatic airway.

作者信息

Wang Ke, Wen Fu-Qiang, Feng Yu-Ling, Ou Xue-Mei, Xu Dan, Yang Jie, Deng Zhi-Pin

机构信息

Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.

出版信息

Cell Biol Int. 2007 Nov;31(11):1388-95. doi: 10.1016/j.cellbi.2007.06.004. Epub 2007 Jun 29.

DOI:10.1016/j.cellbi.2007.06.004
PMID:17698377
Abstract

Asthma is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC1) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of Calcium-activated chloride channel 1 (CaCC1) and mucus overproduction in Chinese asthmatic airway, the expression of CaCC1, mucin 5AC (MUC5AC) and mucus in bronchial tissues were examined. Bronchial tissues were isolated from non-cancerous areas of lungs obtained following resection for lung neoplasm in West China Hospital from April to July in 2004. Six patients were diagnosed lung neoplasm with moderate asthma, and other ten were diagnosed lung neoplasm without asthma as the control subjects. The expression of CaCC1, MUC5AC and mucin in bronchial tissues was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridized with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and Alcian blue-periodic acid Schiff (AB-PAS) staining, respectively. In RT-PCR, two expression patterns of CaCC1 mRNA were found, which were located in the 450 bp and 510 bp. With in situ hybridization, a stronger expression of CaCC1 mRNA was further detected throughout the bronchial tissues from patients with asthma than control subjects (P<0.01); Samples from asthmatics were showed a stronger staining for MUC5AC than those in control subjects (P<0.05); AB-PAS staining revealed more mucins and goblet cells in asthmatic bronchial epithelium and submucosal gland comparing to that in control subjects (P<0.05). The increased expression of CaCC1 in asthmatic airways was well correlated with the expression of MUC5AC protein, the percentage of goblet cells and the area of submucosal gland (P<0.01, P<0.01, P<0.05). These results suggest that the up-regulated gene expression of CaCC1 exists, which is complicated with mucus hyper-secretion in Chinese asthmatic airway.

摘要

哮喘通常伴有气道黏液过度分泌。最近发现人钙激活氯离子通道1(CaCC1)表达增加在哮喘气道黏液过度分泌中起重要作用。为了研究中国哮喘气道中钙激活氯离子通道1(CaCC1)与黏液过度分泌的关系,检测了支气管组织中CaCC1、黏蛋白5AC(MUC5AC)和黏液的表达。支气管组织取自2004年4月至7月在华西医院因肺部肿瘤切除获取的肺部非癌区域。6例被诊断为肺部肿瘤合并中度哮喘的患者,另外10例被诊断为肺部肿瘤但无哮喘的患者作为对照。分别采用逆转录聚合酶链反应(RT-PCR)、地高辛(DIG)标记RNA探针原位杂交、免疫组化及阿尔辛蓝-过碘酸希夫(AB-PAS)染色检测支气管组织中CaCC1、MUC5AC和黏蛋白的表达。在RT-PCR中,发现CaCC1 mRNA有两种表达模式,分别位于450 bp和510 bp处。原位杂交显示,哮喘患者支气管组织中CaCC1 mRNA的表达比对照组更强(P<0.01);哮喘患者样本中MUC5AC染色比对照组更强(P<0.05);AB-PAS染色显示,与对照组相比,哮喘患者支气管上皮和黏膜下腺中的黏蛋白和杯状细胞更多(P<0.05)。哮喘气道中CaCC1表达增加与MUC5AC蛋白表达、杯状细胞百分比及黏膜下腺面积密切相关(P<0.01,P<0.01,P<0.05)。这些结果表明,中国哮喘气道中存在CaCC1基因表达上调,且与黏液高分泌有关。

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