Hepatocyte replicative arrest, hepatic progenitor cells and the ductular reaction in hepatic fibrogenesis

肝细胞复制停滞、肝祖细胞和肝纤维化中的导管反应

• 批准号: nhmrc : 455985
• 负责人: A/Pr Julie Jonsson
• 金额: $ 35.19万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/hepatocyte-replicative-arrest-hepatic-fibrogenesis/77412
• 关键词: Hepatocyte; replicative; arrest; hepatic; progenitor

Chronic liver diseases such as hepatitis C and obesity-related fatty liver can be associated with scarring that eventually results in cirrhosis and liver failure. We are unsure why this scarring occurs, but as hepatitis and fatty liver are becoming more common it is necessary to understand this process so that effective therapies can be developed. This study looks at one possible mechanism to explain the development of liver scarring. We believe that the normal repair mechanisms of the liver lead to the production of liver cells to replace those that have died, but in some circumstances also produce small bile ducts that drain bile from the hepatocytes. These small bile ducts may have a previously unsuspected role in stimulating the scar formation. The study will see if the small bile ducts are produced in a range of liver diseases in humans, and will use rodent models to find the factors responsible for stimulating the scarring. When the process is understood more clearly, it could lead to the development of new or more effective therapies to reduce or even reverse liver scarring.

慢性肝病，如丙型肝炎和肥胖相关的脂肪肝，可能与最终导致肝硬化和肝功能衰竭的疤痕有关。我们不确定为什么会出现这种疤痕，但随着肝炎和脂肪肝变得越来越普遍，有必要了解这一过程，以便开发有效的治疗方法。这项研究着眼于解释肝瘢痕形成的一种可能机制。我们认为，肝脏的正常修复机制会产生肝细胞来取代那些死亡的细胞，但在某些情况下也会产生小胆管，从肝细胞中排出胆汁。这些小胆管可能在刺激疤痕形成方面具有以前未被怀疑的作用。这项研究将观察人类的一系列肝脏疾病是否会产生小胆管，并将使用啮齿动物模型来寻找刺激疤痕形成的因素。当这个过程被更清楚地理解时，它可能会导致新的或更有效的治疗方法的发展，以减少甚至逆转肝疤痕。