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首页> 外文期刊>Physiological Reviews >Respiratory tract mucin genes and mucin glycoproteins in health and disease.
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Respiratory tract mucin genes and mucin glycoproteins in health and disease.

机译：呼吸道粘蛋白基因和粘蛋白糖蛋白在健康和疾病中的作用。

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This review focuses on the role and regulation of mucin glycoproteins (mucins) in airway health and disease. Mucins are highly glycosylated macromolecules (> or =50% carbohydrate, wt/wt). MUC protein backbones are characterized by numerous tandem repeats that contain proline and are high in serine and/or threonine residues, the sites of O-glycosylation. Secretory and membrane-tethered mucins contribute to mucociliary defense, an innate immune defense system that protects the airways against pathogens and environmental toxins. Inflammatory/immune response mediators and the overproduction of mucus characterize chronic airway diseases: asthma, chronic obstructive pulmonary diseases (COPD), or cystic fibrosis (CF). Specific inflammatory/immune response mediators can activate mucin gene regulation and airway remodeling, including goblet cell hyperplasia (GCH). These processes sustain airway mucin overproduction and contribute to airway obstruction by mucus and therefore to the high morbidity and mortality associated with these diseases. Importantly, mucin overproduction and GCH, although linked, are not synonymous and may follow from different signaling and gene regulatory pathways. In section i, structure, expression, and localization of the 18 human MUC genes and MUC gene products having tandem repeat domains and the specificity and application of MUC-specific antibodies that identify mucin gene products in airway tissues, cells, and secretions are overviewed. Mucin overproduction in chronic airway diseases and secretory cell metaplasia in animal model systems are reviewed in section ii and addressed in disease-specific subsections on asthma, COPD, and CF. Information on regulation of mucin genes by inflammatory/immune response mediators is summarized in section iii. In section iv, deficiencies in understanding the functional roles of mucins at the molecular level are identified as areas for further investigations that will impact on airway health and disease. The underlying premise is that understanding thepathways and processes that lead to mucus overproduction in specific airway diseases will allow circumvention or amelioration of these processes.
机译：这篇综述着重于黏蛋白糖蛋白（黏蛋白）在气道健康和疾病中的作用和调节。粘蛋白是高度糖基化的大分子（>或= 50％碳水化合物，wt / wt）。 MUC蛋白主链的特征是许多串联重复序列，其中包含脯氨酸，并且在丝氨酸和/或苏氨酸残基（O-糖基化位点）较高。分泌性和膜拴粘蛋白促进粘膜纤毛防御，粘膜纤毛防御是一种固有的免疫防御系统，可保护呼吸道免受病原体和环境毒素的侵害。炎症/免疫反应介质和粘液的过量产生是慢性气道疾病的特征：哮喘，慢性阻塞性肺病（COPD）或囊性纤维化（CF）。特定的炎症/免疫反应介质可以激活粘蛋白基因调节和气道重塑，包括杯状细胞增生（GCH）。这些过程维持气道粘蛋白的过度生产，并导致粘液阻塞气道，并因此导致与这些疾病相关的高发病率和死亡率。重要的是，粘蛋白过量生产和GCH虽然联系在一起，但不是同义词，可能来自不同的信号传导和基因调控途径。在第一部分中，概述了具有串联重复结构域的18种人类MUC基因和MUC基因产物的结构，表达和定位，以及在气道组织，细胞和分泌物中鉴定粘蛋白基因产物的MUC特异性抗体的特异性和应用。在动物模型系统中，慢性气道疾病中粘蛋白的过量生产和分泌细胞化生在第二部分中进行了综述，并在哮喘，COPD和CF的疾病特定小节中进行了论述。第三部分总结了关于炎症/免疫反应介质对粘蛋白基因调控的信息。在第四节中，认识到在分子水平上对粘蛋白的功能性作用的理解不足是需要进一步研究的领域，这将影响气道健康和疾病。基本前提是，了解导致特定气道疾病中粘液过度产生的途径和过程，将可以规避或改善这些过程。

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