Liver Stem Cell Response to Inflammation and Alcohol

肝干细胞对炎症和酒精的反应

• 批准号: 6791644
• 负责人: IAN N HINES
• 金额: $ 4.3万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791644
• 关键词: alcoholic beverage consumption; alcoholic fatty liver; alcoholic hepatitis; alcoholic liver cirrhosis; carbon tetrachloride; cell proliferation; concanavalin A; disease /disorder model; ethanol; fats; fibrosis; flow cytometry; hepatectomy; immunocytochemistry; immunomagnetic separation; inflammation; laboratory mouse; liver cells; pathology; postdoctoral investigator; stem cells; toxicology

DESCRIPTION (provided by applicant): Alcohol-induced liver injury represents a significant etiology of end-stage liver disease characterized inflammation, fat accumulation, and fibrosis. Because traditional treatment options such as organ transplantation have not been very successful, non-traditional therapies including the use of hepatic progenitor cells (HPC) offer an intriguing alternative. HPC proliferation and differentiation seems to be induced by two critical factors, hepatic insufficiency and a decreased ability of mature hepatocytes to replicate. Here, using two models of HSC proliferation, one initiated by inflammation due to Concanavalin A (ConA) and a second by fibrosis due to carbon tetrachloride (CCI4), each followed by partial hepatectomy, we will first determine whether the type of injury affects the differentiation lineage of HPCs. Next, since alcoholic liver disease (ALD) is complicated by fatty liver, we will determine the effect that fat, due to its reduction in the ability of mature hepatocytes to proliferate in response to injury, has on HPC proliferation in these models. It is hypothesized that fat accumulation will promote endogenous HPC proliferation by inhibition of normal hepatocyte function and proliferation within the inflamed or fibrotic and regenerating liver.

描述（由申请人提供）：酒精引起的肝损伤代表了以炎症、脂肪堆积和纤维化为特征的终末期肝病的重要病因。由于器官移植等传统治疗方案并不是很成功，因此包括使用肝祖细胞 (HPC) 在内的非传统疗法提供了一种有趣的替代方案。 HPC 增殖和分化似乎是由两个关键因素诱导的：肝功能不全和成熟肝细胞复制能力下降。在这里，使用两种 HSC 增殖模型，一种是由刀豆蛋白 A (ConA) 引起的炎症引起的，另一种是由四氯化碳 (CCI4) 引起的纤维化引起的，每种模型随后进行部分肝切除术，我们将首先确定损伤类型是否影响 HPC 的分化谱系。接下来，由于酒精性肝病 (ALD) 会并发脂肪肝，因此我们将确定脂肪对这些模型中 HPC 增殖的影响，因为脂肪会降低成熟肝细胞响应损伤而增殖的能力。据推测，脂肪积累将通过抑制正常肝细胞功能以及发炎或纤维化和再生肝脏内的增殖来促进内源性 HPC 增殖。