Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression
Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression
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DOI：
10.1164/rccm.200311-1529oc
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发表时间：
2004-05-01
影响因子：
24.7
通讯作者：
Fahy, JV
中科院分区：
文献类型：
--
作者：
Woodruff, PG;Dolganov, GM;Fahy, JV
轻度至中度哮喘的支气管高反应性可能是由于气道平滑肌细胞增殖或获得高收缩表型所致。由于这些细胞在轻中度哮喘中还没有得到很好的表征，我们研究了哮喘患者这一亚组中平滑肌细胞的形态和基因表达特征。使用14例轻中度哮喘患者和15例对照组的支气管活检标本，我们采用激光显微切割和两步实时聚合酶链反应，通过体视学和一组与气道平滑肌过度收缩表型相关的基因表达来量化平滑肌细胞形态。我们发现，两组的气道平滑肌细胞大小相似，但哮喘患者的细胞数量几乎高出两倍（p = 0.03），粘膜下层的平滑肌数量增加了50-83%（p < 0.005）。平滑肌细胞的基因表达谱显示，健康受试者和哮喘受试者细胞中编码表型标记物的基因表达无差异（均p > 0.1）。我们的结论是气道平滑肌增生是轻中度哮喘患者的病理特征。然而，轻中度哮喘的平滑肌细胞在体外并没有表现出过度收缩表型的肥大或基因表达变化。
Bronchial hyperresponsiveness in mild to moderate asthma may result from airway smooth muscle cell proliferation or acquisition of a hypercontractile phenotype. Because these cells have not been well characterized in mild to moderate asthma, we examined the morphometric and gene expression characteristics of smooth muscle cells in this subgroup of patients with asthma. Using bronchial biopsies from 14 subjects with mild to moderate asthma and 15 control subjects, we quantified smooth muscle cell morphology by stereology and the expression of a panel of genes related to a hypercontractile phenotype of airway smooth muscle, using laser microdissection and two-step real-time polymerase chain reaction. We found that airway smooth muscle cell size was similar in both groups, but cell number was nearly twofold higher in subjects with asthma (p = 0.03), and the amount of smooth muscle in the submucosa was increased 50-83% (p < 0.005). Gene expression profiling in smooth muscle cells showed no difference in the expression of genes encoding phenotypic markers in cells from healthy subjects and subjects with asthma (all p > 0.1). We conclude that airway smooth muscle proliferation is a pathologic characteristic of subjects with mild to moderate asthma. However, smooth muscle cells in mild to moderate asthma do not show hypertrophy or gene expression changes of a hypercontractile phenotype observed in vitro.