Regulation of NF-kB by the ZO-1/ZONAB pathway

ZO-1/ZONAB 通路对 NF-kB 的调节

• 批准号: G0700743/1
• 负责人: Karl Matter
• 金额: $ 55.75万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0700743%2F1
• 关键词: Regulation; NF; kB; ZO; ZONAB

Epithelia are continuous layers of cells that delineate our tissues and organs. The integrity of epithelia is important for our organs to function normally and to protect us from our environment. For example, breaches in epithelial layers such as the skin or in the lining of the intestine can lead to serious infections. Individual epithelial cells interact with each other via molecular complexes that mediate adhesion but also function as sensors that transmit information about the environment, such as the presence or absence of neighbouring cells, to the cell interior. These sensors are important for the regulation of cell behaviour as they tell cells when to divide and when to stop to grow. If an epithelium is damaged, for example, cells divide and migrate to repair holes until they reach their neighbours and can form new adhesive complexes. Therefore, defects in these sensory mechanisms lead to severe diseases such as cancer. Many inflammatory diseases affect the functional properties of these adhesive molecular complexes. These diseases can be caused by bacteria and viruses, as well as allergens or by our own body defence system and often directly involve components of adhesive complexes. For example, a bacterium that causes gastric cancer injects molecules into epithelial cells that stimulate dissociation of adhesive complexes. Such infections also cause a cellular inflammatory response that helps our body to deal with them. However, these cellular responses can get out of control and cause damage. Here we focus on a new molecular mechanism by which adhesive complexes in epithelial cells can regulate the cellular inflammatory response. We propose to study the molecular mechanism and to determine how it is affected in two models of human disease. One model is based on the mentioned bacterium that causes gastric cancer and the other on cells isolated from colon and prostate cancers. Understanding how adhesive complexes guide the inflammatory response will help us to design new therapies for the above-mentioned diseases.

上皮是描绘我们组织和器官的细胞的连续层。上皮的完整性对于我们的器官正常运作并保护我们免受环境很重要。例如，诸如皮肤或肠壁上的上皮层中的漏洞会导致严重的感染。单个上皮细胞通过介导粘附的分子复合物相互相互作用，并且还充当传递有关环境信息的传感器，例如存在或不存在相邻细胞的信息，以传递到细胞内部。这些传感器对于调节细胞行为很重要，因为它们告诉细胞何时分裂以及何时停止生长。例如，如果上皮受损，例如，细胞会分裂并迁移以修复孔，直到到达邻居并可以形成新的粘合剂复合物为止。因此，这些感觉机制的缺陷导致严重疾病，例如癌症。许多炎症性疾病会影响这些粘合分子复合物的功能特性。这些疾病可能是由细菌和病毒，过敏原或我们自己的身体防御系统引起的，并且通常直接涉及粘合剂复合物的成分。例如，导致胃癌的细菌将分子注射到刺激粘合剂复合物解离的上皮细胞中。这种感染还会引起细胞炎症反应，帮助我们的身体应对它们。但是，这些细胞反应可能失控并造成损害。在这里，我们关注一种新的分子机制，通过该机制，上皮细胞中的粘合剂复合物可以调节细胞炎症反应。我们建议研究分子机制，并确定在两种人类疾病模型中如何影响它。一种模型基于上述细菌，该细菌会导致胃癌，另一个基于从结肠和前列腺癌分离的细胞。了解粘合剂复合物如何指导炎症反应将有助于我们设计上述疾病的新疗法。