Mucin gene expression during differentiation of human airway epithelia in vitro -: MUC4 and MUC5B are strongly induced

Mucin gene expression during differentiation of human airway epithelia in vitro -: MUC4 and MUC5B are strongly induced
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DOI:
10.1165/ajrcmb.20.4.3442
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发表时间:
1999-04-01
影响因子:
6.4
通讯作者:
Randell, SH
Randell, SH
中科院分区:
医学1区
文献类型:
--
作者:
Bernacki, SH;Nelson, AL;Randell, SH

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粘液高分泌是慢性气道疾病的特征。然而,人们对监管机制知之甚少。人气道上皮细胞在气液界面(ALI)处的可渗透支持物上生长,形成类似于体内发现的粘膜纤毛形态。这样的培养物提供了用于研究分泌细胞谱系、分化和功能的模型,并且可以提供关于导致粘液分泌过多的事件的见解。培养的分化良好的人气道上皮细胞的粘蛋白基因表达谱尚未建立。我们比较了所有目前描述的粘蛋白基因在低分化(传统文化塑料)和分化良好(ALI)的人鼻和支气管上皮细胞的表达。逆转录-聚合酶链反应(RT-PCR)证实了MUC 3、MUC 5AC、MUC 5 B和MUC 6信使RNA(mRNA)的分化依赖性上调。北方印迹分析显示MUC 4的类似增加,并证明MUC 4和MUC 5 B表达的诱导依赖于视黄酸。MUC 1,MUC 2,MUC 7和MUC 8 mRNA也通过RT-PCR检测到,但这些基因似乎没有强烈的调节分化的功能。粘蛋白基因表达在支气管和鼻腔细胞中相似。因此,体外人气道上皮细胞的粘膜纤毛分化需要上调几种粘蛋白基因。
Mucus hypersecretion is characteristic of chronic airway diseases. However, regulatory mechanisms are poorly understood. Human airway epithelial cells grown on permeable supports at the air-liquid interface (ALI) develop a mucociliary morphology resembling that found in vivo. Such cultures provide a model for studying secretory cell lineage, differentiation, and function, and may provide insight regarding events leading to mucus hypersecretion. The mucin gene expression profile of well-differentiated human airway epithelial cells in culture has not yet been established. We compared expression of all the currently de scribed mucin genes in poorly differentiated (conventional cultures on plastic) and well-differentiated (ALI) human nasal and bronchial epithelial cells. Differentiation-dependent upregulation of MUC3, MUC5AC, MUC5B, and MUC6 messenger RNA (mRNA) was demonstrated using reverse transcriptase-polymerase chain reaction (RT-PCR). Northern blot analysis showed a similar increase for MUC4 and demonstrated that induction of MUC4 and MUC5B expression depended on retinoic acid. MUC1, MUC2, MUC7, and MUC8 mRNAs were also detected by RT-PCR, but these genes did not appear to be strongly regulated as a function of differentiation. Mucin gene expression was similar in bronchial and nasal cells. Thus, mucociliary differentiation of human airway epithelia in vitro entails upregulation of several mucin genes.