BRONCHIAL SECRETIONS: PHYSICAL & CHEMICAL STUDIES

粘蛋白糖蛋白(粘蛋白)，粘膜层的主要成分 保护和润滑哺乳动物的呼吸道，由 上皮细胞排列在管腔和粘膜下腺内。这些细胞 慢性阻塞性肺病的腺体和腺体表现为增生 疾病。人们对启动或关闭的机制或因素知之甚少 调节化生和增生，尽管它最近被 认为粘蛋白基因转录的启动是通过 大鼠呼吸道浆液细胞是导致高脚杯和 粘液细胞化生和高分泌(1)。现有证据 表明几种粘蛋白基因在呼吸道和呼吸道中都有表达 肠子。我们推测，特定的粘蛋白蛋白 在呼吸道疾病中高表达(可能由特定的呼吸道细胞) 而呼吸道粘蛋白基因家族的不同成员 为特定的糖基转移酶提供独特的底物。 我们研究计划的长期目标是阐明这一角色 呼吸道粘蛋白在健康和疾病中的作用。我们最近确认了 并鉴定了编码人tbm的cdna克隆 气管、支气管壁的粘蛋白似乎是呼吸道特异性的。具体的 这项建议的目的是：[1]确定和表征全长 TBM编码基因的克隆及其异同 当这样的信息变得可用时，就会转移到其他粘蛋白。[2]澄清 用原位杂交技术研究粘蛋白基因的细胞和组织特异性 并进行Northern印迹分析，确定其是否表达 特定的粘蛋白基因在呼吸道疾病中受到影响。[3]隔离和 鉴定结核分枝杆菌的基因组DNA。结核分枝杆菌编码基因的克隆 将被用来探测基因组文库。TBM基因组克隆将是 以染色体定位、限制图谱、S1图谱为特征， 并通过外显子/内含子边界的序列分析。[4]至 研究TbM基因的表达和调控。我们会 测定TbM基因的转录活性。如果它被证明 基因组克隆的启动子序列具有转录活性 将使用以下方法研究AIM[3]中确定的调控元素 启动子缺失构建。

Mucin glycoproteins (mucins), the major components of the mucosal layer that protects and lubricates mammalian airways, are secreted by epithelial cells lining the lumen and submucosal glands. These cells and glands exhibit hyperplasia in chronic obstructive pulmonary diseases. Little is known about the mechanism or factors initiating or regulating metaplasia and hyperplasia, although it has recently been proposed that initiation of transcription of mucin protein genes by serous cells in rat airways is a primary event leading to goblet and mucous cell metaplasia and hypersecretion (1). Current evidence indicates that several mucin genes are expressed both in the airways and intestine. We speculate that the specific mucin proteins are more highly expressed in airway diseases (perhaps by specific airway cells) and that different members of the airway mucin protein gene family provide unique substrates for specific glycosyltransferases. The long term objective of our research program is to elucidate the role of airway mucins in health and in diseases. We have recently identified and characterized a cDNA clone that encodes TBM, a human tracheobronchial mucin that appears to be airway-specific. The specific aims of this proposal are: [1] To identify and characterize full length cDNA clones encoding TBM and to delineate similarities and differences to other mucins as such information becomes available. [2] To elucidate the cell and tissue specificity of mucin genes by in situ hybridization and Northern blot analysis and determine whether the expression of specific mucin genes is affected in airway diseases. [3] To isolate and characterize genomic DNA for TBM. The cDNA clone that encodes for TBM will be used to probe genomic libraries. TBM genomic clones will be characterized by chromosomal location, restriction mapping, S1 mapping, and by sequence analysis of the exon/intron boundaries. [4] To investigate expression and regulation of the TBM gene. We will determine the transcriptional activity of the TBM gene. Should it prove transcriptionally active, the promoter sequences of the genomic clones identified in aim [3] will be studied for regulatory elements using promoter deletion constructs.