Zebrafish: an important tool for liver disease research.

Zebrafish: an important tool for liver disease research.
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DOI:
10.1053/j.gastro.2015.08.034
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发表时间:
2015-11
期刊:
影响因子:
29.4
通讯作者:
Sadler KC
Sadler KC
中科院分区:
医学1区
文献类型:
--
作者:
Goessling W;Sadler KC

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随着肝胆疾病发病率的增加,我们必须提高对导致肝病发病的分子、细胞和生理因素的认识。动物模型帮助我们确定疾病机制,可能有针对性的治疗。传统上,斑马鱼被用于研究胚胎发育,但对肝脏疾病的研究也很重要。斑马鱼胚胎发育迅速;所有的消化器官在5日龄的幼虫中成熟。在这一阶段,它们可发展为由发育缺陷或毒素或乙醇引起的损伤引起的肝胆疾病,并在数周内出现癌前病变。斑马鱼的肝细胞组成、功能、信号传导、对损伤的反应以及介导肝脏疾病的细胞过程与人类相似。人类和斑马鱼之间的基因高度保守,使它们成为研究肝脏疾病基本机制的有用系统。我们可以通过基因筛选来识别参与特定疾病过程的新基因,通过化学筛选来识别作用于特定过程的途径和化合物。我们回顾了斑马鱼的研究如何提高了我们对遗传性和获得性肝脏疾病以及肝癌和再生的理解。
As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration.