气道黏蛋白的结构及其基因表达的调节

黏蛋白（mucin,MUC）是具有特征性串联重复区（tandem repeat,TR）区域的糖蛋白。这些TR区域富含丝氮酸或苏氯酸以及脯氨酸。MUC骨架由MUC基因编码．其中已有20种人类MUC基因存最近二十年通过DNA重组技术被确认。大多数TR丝氨酸／苏氨酸残基都被O-糖基化。MUC5AC和MUC5B是气道中最主要的两种MUC,它们的TR在蛋白质骨架中分别重复4、5倍。这些重复的TR被富集的半胱氯酸分隔．其中每个TR包含脯氮酸、丰富的丝／苏氨酸残基和O-糖基化位点,TR序列可重复成百上千．而每个TR中可含有数百个O-糖链结合位点．故MUC蛋白质骨架的TR数目决定MUC大小,并且O-糖链的添加可使MUC构型发生改变。因此TR可直接或间接地造成MUC构象和功能的多样性。TR和连接的O-糖链可影响MUC的大小、形状和质量．从而形成黏液本身不同的生物物理学和生物学性质。MUC是黏膜免疫学的先天性防御系统,这个观点．在不断地得到更多的支持。MUCSAC和MUCSB足健康气道黏液和慢性气道疾病患苦痰液的主要组分。几种炎症性气道疾病有共同的途径：MUC基因表达增加、杯状细胞增生和（或）黏膜下腺肥大。每个过程都可能造成支气管哮喘、慢性阻塞性肺疾病或囊性纤维病患者气道MUC过度产生和黏液梗阻。过去十年里,我们对这些变化的病理生理机制研究已有了显著进步。相关因子如生长因子、免疫／炎症介质、环境刺激因素、病原等可通过丝裂原激活的蛋白激酶、表皮中长因子受体等不同的细胞信号转导通路在转录（mRNA）和（或）转录后水平（如精基化）对其进行调节有差别地调节MUC基因表达。

Airway mucins:structure and regulation of gene expression

Mucins (MUC) are glycoproteins characterized by tandem repeat (TR) domains that are high in proline and scrine or threonine.A MUC protein backbone is encoded by a MUC gene,of which 20 human MUC genes have been identified by recombinant DNA technology over the last two decades.A majority of the TR serine/threonine residues are O-glycosylated.MUC5AC and MUC5B are two of the most important airway MUC,in protein backbone of which TR repeats 4,5 times.These duplicate TR has been separated by enriched cysteine,each of which contains proline,rich serine/threonine residues and O-glycosylation sites.TR sequence is repeated hundred times,each of which contains hundreds of O-glycosylation sites,so the size of MUC is determined by the number of TR and the structure of MUC can be changed as O-glycosides is added to.Therefore the conformation and function of MUC vary because of TR directly or indirectly.TR and attached O-glycosides can affect the size,shape and quality of MUC,and thus they cause mucus own different properties of biophysical and biological.The concept that MUC function as part of the innate immune defensive systems that protect the airway epithelium against pathogens and environmental agents in the airways continues to gain validity.The MUC5AC and MUC5B are major components of airway mucus from healthy airways and sputum from patients with chronic airway diseases.Several inflammatory airway diseases share common pathways of increased MUC gene expression,goblet cell proliferation and submucosal gland hypertrophy;each process can contribute to MUC overproduction and mucus obstruction in the conducting airways of patients with asthma,chronic obstructive pulmonary diseases or cystic fibrosis.There have been significant advances in our understanding of pathophysiological mechanisms leading to these findings over the last decade.Specific mediators,such as growth factors,inflammatory/immune response mediators,pollutants,and infection,differentially regulate MUC genes through various intracellular signaling pathways such by activating transcriptional and(or)post transcriptional programs that regulate increased rnucin production.