Zebrafish: An Important Tool for Liver Disease Research

Abstract

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.

Three-dimensional structural analysis reveals a Cdk5-mediated kinase cascade regulating hepatic biliary network branching in zebrafish

“…Zebrafish has emerged as an excellent model to study human liver diseases (Goessling and Sadler, 2015). In zebrafish, the intrahepatic biliary network starts developing at 2 days post fertilization (dpf ), before the biliary system starts to function at 5 dpf (Lorent et al, 2010;Sakaguchi et al, 2008).…”

Making It New Again

“…From these basic studies, several insights have emerged that have informed our understanding of disease. There are extensive recent reviews on the use of zebrafish to study liver disease (Goessling and Sadler, 2015; Grompe, 2014; Wilkins and Pack, 2013b). Here, we focus on the intersection between development and regeneration and focus on biliary disease as an illustrative example of how the basic processes of development have promoted our understanding of liver disease.…”

“…All of these functions are conserved from mammals to fish and work in zebrafish on liver development and disease over the last decade has complimented nearly a century of work in mammalian systems. These topics have recently been reviewed by experts in the field (Goessling and Sadler, 2015; Goessling and Stainier, 2016; Wilkins and Pack, 2013a). …”

Inhibition of vascular endothelial growth factor signaling facilitates liver repair from acute ethanol-induced injury in zebrafish

“…The teleost zebrafish show liver injury when exposed to ethanol in their water (Howarth et al, 2011; Jang et al, 2012; Lin et al, 2015; Passeri et al, 2009; Tran et al, 2015; Yin et al, 2012). Studying chronic alcoholic liver injury is difficult in adult zebrafish as they do not feed properly upon ethanol exposure (Goessling and Sadler, 2015). However, the larvae have been proven to be particularly useful for studying acute alcoholic liver injury (Howarth et al, 2011, 2013; Passeri et al, 2009; Yin et al, 2012).…”