Defining the functional roles of MUC5AC and MUC5B in mucus in respiratory airways

定义呼吸道粘液中 MUC5AC 和 MUC5B 的功能作用

• 批准号: G1000450/1
• 负责人: David Thornton
• 金额: $ 47万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000450%2F1
• 关键词: Defining; functional; roles; MUC5AC; MUC5B

Mucus is the jelly-like substance produced by the lungs to defend the body against pollution, bacteria, viruses and other environmental agents. Mucus acts to trap environmental agents and their removal from the lung is made possible by what is known as the ?mucociliary escalator?: Cells lining the surface of the large airways have tiny hairs called cilia which interact with mucus to trap and remove debris from the lungs. The beating action of the cilia moves the mucus up to the throat, where it is swallowed. Individuals suffering from airway diseases such as asthma, cystic fibrosis and chronic bronchitis face the constant struggle of not only making too much mucus, but that the mucus produced is stickier than normal. Such sticky mucus cannot be moved by the cilia, resulting in the airways becoming blocked.Mucus is a complex viscous mixture made up of electrolytes, water and extremely large, rope-like molecules called mucins. There are two types of mucins in the mucus of the large airways, MUC5AC and MUC5B. In disease we know that there is a much larger amount of both mucins produced, which contributes to blocking the airways. In addition, recent research suggests that the ratio of MUC5AC and MUC5B in the mucus gel can alter how the mucus is moved by cilia, but exactly how this happens is not currently understood.In light of this, our principal research question is: Do the two mucins, MUC5AC and MUC5B, make mucus gels which can be moved by cilia with equal efficiency, and do other components of the mucus gel interact with the mucins to alter how mucus is moved?To answer this question, we are bringing together research teams in Biology and Physics in order to understand the distinct contributions of MUC5AC and MUC5B to the stickiness of the mucus gel. We will also find out what other molecules are critical for creating a moveable mucus gel which can be cleared from the airways. Understanding the organisation of mucus gels in health and disease will enable the design of new treatments for people suffering with airway obstruction.

粘液是肺部产生的类粘液物质，用于保护身体免受污染、细菌、病毒和其他环境因素的侵害。粘液的作用是捕获环境因子，并通过所谓的肺内分泌系统将其从肺中清除。粘液纤毛自动扶梯？：排列在大气道表面的细胞具有称为纤毛的微小毛发，其与粘液相互作用以捕获并清除肺部的碎片。纤毛的跳动将粘液移到喉咙，在那里被吞咽。患有哮喘、囊性纤维化和慢性支气管炎等气道疾病的个体不仅面临着制造过多粘液的持续斗争，而且所产生的粘液比正常情况下更粘稠。这种粘性粘液不能被纤毛移动，导致气道阻塞。粘液是一种复杂的粘性混合物，由电解质，水和非常大的绳状分子（称为粘蛋白）组成。在大气道的粘液中存在两种类型的粘蛋白，MUC5AC和MUC5B。在疾病中，我们知道有大量的两种粘蛋白产生，这有助于阻塞气道。此外，最近的研究表明，粘液凝胶中MUC5AC和MUC5B的比例可以改变纤毛移动粘液的方式，但目前还不清楚这是如何发生的。鉴于此，我们的主要研究问题是：MUC5AC和MUC5B这两种粘蛋白是否能以同样的效率产生能被纤毛移动的粘液凝胶，粘液凝胶的其他成分是否与粘蛋白相互作用以改变粘液的移动方式？为了回答这个问题，我们将生物学和物理学的研究团队聚集在一起，以了解MUC5AC和MUC5B对粘液凝胶粘性的不同贡献。我们还将发现哪些其他分子对于产生可从气道清除的可移动粘液凝胶至关重要。了解粘液凝胶在健康和疾病中的组织将有助于为患有气道阻塞的人设计新的治疗方法。