Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway
Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway
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DOI：
10.1164/ajrccm.165.8.2107068
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发表时间：
2002-04-15
影响因子：
24.7
通讯作者：
Fujino, M
中科院分区：
文献类型：
--
作者：
Hoshino, M;Morita, S;Fujino, M
粘液分泌过多是哮喘的一个临床特征。 Ca2+ 激活的 Cl- 通道 1 (CaCC1) 已被确定为一种在肠上皮细胞中表达的蛋白质，在液体和电解质转运中发挥重要作用。最近，其小鼠对应物 gob-5 被确定为通过粘液过量产生诱导小鼠哮喘的关键分子。为了阐明 CaCC1 与人类哮喘的关系，我们使用实时定量聚合酶链反应分析检测了哮喘患者和正常对照受试者的支气管组织中 CaCC1 的表达。与对照组相比，支气管哮喘患者的 CaCC1 表达显着上调。原位杂交和免疫组化分析表明CaCC1位于支气管上皮，尤其是产生粘液的杯状细胞中。将 CaCC1 表达载体体外转染至人粘液表皮样细胞系 NCl-H292 中，增加粘液产生并诱导 MUC5AC 基因。这些结果表明，CaCC1 在杯状细胞的粘液产生和分化中发挥直接作用，并可能通过其粘液诱导活性促进哮喘的发病机制。
Mucus overproduction is a clinical feature of asthma. Ca2+ activated Cl- channel 1 (CaCC1) has been identified as a protein that is expressed in intestinal epithelia and that plays an important role in fluid and electrolyte transport. Recently, its mouse counterpart, gob-5, was identified as a key molecule in the induction of murine asthma through mucus overproduction. To elucidate the relationship of CaCC1 to human asthma, we examined CaCC1 expression using real-time quantitative polymerase chain reaction analysis in bronchial tissues from patients with asthma and normal control subjects. The expression of CaCC1 was significantly upregulated in patients with bronchial asthma compared with control subjects. In situ hybridization and immunohistochemical analysis demonstrated that CaCC1 is located in the bronchial epithelium, especially in mucus-producing goblet cells. In vitro transfection of a CaCC1 expression vector into the human mucoepidermoid cell line, NCl-H292, increased mucus production and induced the MUC5AC gene. These results suggest that CaCC1 plays a direct role in mucus production and differentiation in goblet cells and may contribute to the pathogenesis of asthma through its mucus-inducing activity.