The Influence of Mechanical Strain on Hepatic Stellate Cell Function in Relation to the Development of Hepatic Fibrosis

机械应变对肝星状细胞功能与肝纤维化发展的影响

• 批准号: G0700582/1
• 负责人: Timothy Gordon-Walker
• 金额: $ 29.96万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=G0700582%2F1
• 关键词: Influence; Mechanical; Strain; Hepatic; Stellate

Liver scarring (fibrosis) and cirrhosis (end-stage scarring) are the consequence of virtually all long-term liver diseases that cause inflammation. These include inborn metabolic disorders, toxic damage, immune conditions and viral infections. Each year in the United Kingdom, approximately 4000 people die due to the consequences of cirrhosis, two-thirds of whom are aged under-65. At present, liver transplantation is the only definitive treatment but unfortunately its availability is severely limited. We must therefore develop new treatments to prevent and reverse liver fibrosis. Tissue swelling is an early part of injury and leads to the stretching of cells, which we believe contributes to the development of liver fibrosis. We know that the livers of children with congenital heart disease become congested, or stretched, leading to liver fibrosis and cirrhosis. We intend to use models of liver stretch in order to understand why this should happen and how it might be prevented. It is likely that these results could be used to understand how many different disorders cause liver and tissue scarring, leading to the development of new treatments. The research will be conducted in the MRC Centre for Inflammation Research under the supervision of Professor Iredale, a leading expert in liver fibrosis.

肝脏疤痕（纤维化）和肝硬化（终末期疤痕）是几乎所有引起炎症的长期肝脏疾病的结果。这些包括先天性代谢紊乱、毒性损伤、免疫状况和病毒感染。英国每年约有 4000 人死于肝硬化，其中三分之二年龄在 65 岁以下。目前，肝移植是唯一确定的治疗方法，但不幸的是其可用性受到严重限制。因此，我们必须开发新的治疗方法来预防和逆转肝纤维化。组织肿胀是损伤的早期部分，会导致细胞拉伸，我们认为这会导致肝纤维化的发展。我们知道患有先天性心脏病的儿童的肝脏会充血或拉伸，导致肝纤维化和肝硬化。我们打算使用肝脏拉伸模型来了解为什么会发生这种情况以及如何预防。这些结果很可能可用于了解有多少种不同的疾病会导致肝脏和组织疤痕，从而开发新的治疗方法。该研究将在肝纤维化领域权威专家 Iredale 教授的监督下在 MRC 炎症研究中心进行。