Evaluating the importance of autophagy/xenophagy in protecting the intestinal epithelium in Crohn s Disease

评估自噬/异体自噬在保护克罗恩病肠上皮中的重要性

• 批准号: G0800759/1
• 负责人: Jack Satsangi
• 金额: $ 42.11万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800759%2F1
• 关键词: Evaluating; importance; autophagy; xenophagy; protecting

The inflammatory bowel diseases (IBD) are disabling life-long illnesses which are common in the Western world. Typical symptoms common to both illnesses include abdominal pain, weight loss, and diarrhoea. There are two main types of inflammatory bowel disease: Crohn?s disease (CD) and ulcerative colitis (UC). The cause of these illnesses is not certain, but it is now very clear that each condition is influenced by a number of genetic risk factors as well as environmental factors. These include the presence of bacteria in the bowel and smoking habit. Recently, great progress has been made in identifying several new genetic risk factors involved in Crohn?s disease. Two of the most recently identified genes are involved in a process called autophagy, a mechanism by which cells conserve or recycle specific proteins to keep themselves alive in conditions of starvation, or under specific environmental ?stressors?. There is some evidence that autophagy might also be involved in the maintenance of a healthy gut, removing or killing ?bad? bacteria and allowing ?good? bacteria to live there. Changes in the regulation of the autophagy pathway might upset this delicate balance or allow ?good? bacteria to produce unwanted responses from the gut cells, leading to inflammation. In a series of laboratory experiments, we aim to investigate this pathway and to clarify how function is changed in CD patients and the effect of different environmental ?stressors?, and of genetic alterations. Results will indicate whether this pathway is involved in the cause or development of CD and may also indicate the molecular pathways involved which could potentially lead to the development of new drug therapy.

炎症性肠病（IBD）是在西方世界常见的致残性终身疾病。这两种疾病共同的典型症状包括腹痛、体重减轻和腹泻。有两种主要类型的炎症性肠病：克罗恩病？S病（CD）和溃疡性结肠炎（UC）。这些疾病的原因尚不确定，但现在很清楚，每种疾病都受到许多遗传风险因素和环境因素的影响。这些因素包括肠道中存在细菌和吸烟习惯。最近，在确定克罗恩病的几个新的遗传危险因素方面取得了很大进展？的疾病。最近发现的两个基因参与了一个称为自噬的过程，这是一种细胞保存或回收特定蛋白质以使自己在饥饿或特定环境条件下存活的机制。压力源？有一些证据表明，自噬也可能参与维持健康的肠道，去除或杀死？不好吗？细菌和允许？好了吗？细菌在那里生存。自噬途径调节的变化可能会打破这种微妙的平衡，还是允许？好吗？细菌从肠道细胞产生不必要的反应，导致炎症。在一系列的实验室实验中，我们的目的是调查这一途径，并澄清如何改变功能的CD患者和不同的环境？压力源？和基因改变。结果将表明该途径是否参与CD的病因或发展，还可能表明可能导致新药治疗开发的分子途径。