Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis
Promoter analysis and aberrant expression of the MUC5B gene in diffuse panbronchiolitis
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DOI：
10.1164/rccm.200409-1168oc
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发表时间：
2005-05-01
影响因子：
24.7
通讯作者：
Keicho, N
中科院分区：
文献类型：
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作者：
Kamio, K;Matsushita, I;Keicho, N
弥漫性泛细支气管炎（DPB）是一种主要影响亚洲人群的慢性炎症性气道疾病。DPB被认为是一种复杂的遗传性疾病。考虑到该疾病的粘液分泌过多，我们假设黏液蛋白基因的转录活性可能在DPB中发生改变。我们分析了6个粘蛋白基因muc1、MUC2、MUC4、MUC5AC、MUC5B和muc7调控区的核苷酸序列，并检测了它们的启动子多态性。其中MUC5B基因中发现的插入/删除多态性与疾病显著相关（p = 0.0001）。在三种主要启动子单倍型中观察到的转录活性与这些单倍型所涉及的疾病关联的强度相对应。DPB肺组织免疫组化显示，MUC5B不仅在支气管腺中大量表达，而且在支气管表面的杯状细胞数量增加，其中MUC5AC占主导地位，而MUC5B在正常肺中普遍缺乏表达。在DPB中观察到明显的粘液分泌增多，部分原因可能是MUC58的表达增加和异常。MUC5B基因可能参与DPB的发生。MUC5B多态性在其发病机制中的作用有待进一步研究。
Diffuse panbronchiolitis (DPB) is a chronic inflammatory airway disease predominantly affecting Asian populations. DPB is considered to be a complex genetic disease. Considering the mucous hypersecretion of the disease, we hypothesized that the transcriptional activity of mucin genes may be altered in DPB. We analyzed nucleotide sequences of regulatory region of six mucin genes-MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7-and detected their promoter polymorphisms. Among them, the insertion/deletion polymorphism identified in the MUC5B gene was significantly associated with the disease (p = 0.0001). Transcriptional activity observed in the three major promoter haplotypes corresponded to the strength of the disease association in which these haplotypes are involved. Immunohistochemistry of the lung tissues of DPB revealed that MUC5B was abundantly expressed not only in bronchial glands but also in increased numbers of goblet cells on the bronchial surface, where MUC5AC is predominant and MUC5B expression is generally scarce in the normal lung. Marked mucous hypersecretion observed in DPB may be partly explained by increased and aberrant expression of MUC58. The possible involvement of MUC5B gene in DPB was demonstrated. A further role of the MUC5B polymorphism in its pathogenesis should be studied in the future.