MUC5 MUCINS AND AIRWAY DISEASES

描述：（改编自申请人摘要）： 气道粘液层覆盖上皮细胞，提供保护性 对感染因子的屏障，并参与粘膜 对炎症和感染的反应。生理化学和 粘液的生物学特性主要由粘蛋白赋予 糖蛋白（粘蛋白）-大的，高度O-糖基化的，粘性的， 粘弹性大分子粘蛋白是高分泌的 慢性阻塞性肺疾病患者的呼吸道感染和炎症 阻塞性肺疾病粘蛋白分泌过多意味着 MUC基因的上调。9个MUC基因中有7个被鉴定为 date在呼吸道组织和细胞中表达，MUC 4， MUC 5、MUC 5 B和MUC 8基因似乎正常表达良好， 分泌性粘蛋白基因MUC 2和MUC 5的表达似乎是 在感染和气道疾病中改变，至少在囊性 纤维化罗斯博士的长期目标是阐明 由MUC 5基因编码的分泌性粘蛋白在气道健康和疾病中的作用。 MUC 5通常表现出组织和细胞特异性，似乎是 在气道疾病中的差异表达。总的假设是 MUC 5基因的调节和MUC 5粘蛋白的表达影响了 慢性阻塞性肺疾病的发病机制。到 为了解决这一假设，罗斯博士将[1]比较 MUC 5基因的转录单位; [2]表征 MUC 5的气道细胞特异性和白细胞介素反应元件 启动子; [3]确定MUC 5是否在体外受特异性 炎症介质和MUC 5表达和MUC 5粘蛋白 阻塞性肺疾病患者的肺内分泌发生改变; [4] MUC 5粘蛋白的结构/功能。MUC 5基因的研究进展 MUC 5的结构/功能特性的调节和 基因产物可能最终提供防止粘蛋白 阻塞性肺疾病高分泌与规避粘液阻塞 疾病

DESCRIPTION: (Adapted from the Applicant's Abstract): The airway mucus layer coats the epithelium, provides a protective barrier against infectious agents, and participates in the mucosal response to inflammation and infection. The physiochemical and biological properties of mucus are largely conferred by mucins glycoproteins (mucins) - large, highly O-glycosylated, sticky, viscoelastic macromolecules. Mucins are hypersecreted in response to infection and inflammation and obstruct the airway in chronic obstructive pulmonary diseases. Mucin hypersecretion implies upregulation of MUC genes. Seven of the nine MUC genes identified to date are expressed in respiratory tract tissues and cells and MUC4, MUC5, MUC5B, and MUC8 genes appear to be well-expressed normally while expression of the secretory mucin genes MUC2 and MUC5 appear to be altered by infection and in airway diseases, at least in cystic fibrosis. Dr. Rose's long term objective is to elucidate the role of secretory mucins encoded by the MUC5 gene in airway health and diseases. MUC5, which normally exhibits tissue and cell-specificity, seems to be differentially expressed in airway diseases. The overall hypothesis is that regulation of the MUC5 gene and expression of MUC5 mucins impact on the pathogenesis of chronic obstructive pulmonary diseases. To address this hypothesis, Dr. Rose will [1] compare the characterization of the transcriptional unit of the MUC5 gene; [2] characterize the airway cell specificity and interleukin-responsive elements of the MUC5 promoter; [3] determine whether MUC5 is regulated in vitro by specific inflammatory mediators and whether MUC5 expression and MUC5 mucin production are altered in obstructive pulmonary diseases; [4] initiate structure/function of MUC5 mucins. An understanding of MUC5 gene regulation and of the structure/function characteristics of the MUC5 gene products may ultimately provide strategies to prevent mucin hypersecretion and circumvent mucus obstruction in obstructive pulmonary diseases.