Using Zebrafish to Model Liver Diseases-Where Do We Stand?

Pham, Duc-Hung; Zhang, Chang-wen; Yin, Chunyue

doi:10.1007/s40139-017-0141-y

Cited by 34 publications

(27 citation statements)

References 143 publications

(122 reference statements)

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“…• All major mammalian liver cell types are present except Kupffer cells, cell type-specific functions are largely conserved (Goessling and Sadler, 2015;Pham et al, 2017) • Bile secretion via bile canaliculi (Goessling and Sadler, 2015;Pham et al, 2017) • Kupffer cells are not observed (Goessling and Sadler, 2015;Pham et al, 2017) • Different cellular architecture (i.e., hepatocytes arranged into tubules, lobules and portal triads not present; Goessling and Sadler, 2015;Pham et al, 2017) Pancreas…”

Section: Geneticsmentioning

confidence: 99%

Modeling Lysosomal Storage Diseases in the Zebrafish

Peterson

2020

Front. Mol. Biosci.

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Lysosomal storage diseases (LSDs) are a family of 70 metabolic disorders characterized by mutations in lysosomal proteins that lead to storage material accumulation, multipleorgan pathologies that often involve neurodegeneration, and early mortality in a significant number of patients. Along with the necessity for more effective therapies, there exists an unmet need for further understanding of disease etiology, which could uncover novel pathways and drug targets. Over the past few decades, the growth in knowledge of disease-associated pathways has been facilitated by studies in model organisms, as advancements in mutagenesis techniques markedly improved the efficiency of model generation in mammalian and non-mammalian systems. In this review we highlight non-mammalian models of LSDs, focusing specifically on the zebrafish, a vertebrate model organism that shares remarkable genetic and metabolic similarities with mammals while also conferring unique advantages such as optical transparency and amenability toward high-throughput applications. We examine published zebrafish LSD models and their reported phenotypes, address organismspecific advantages and limitations, and discuss recent technological innovations that could provide potential solutions.

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Section: Geneticsmentioning

confidence: 99%

Modeling Lysosomal Storage Diseases in the Zebrafish

Peterson

2020

Front. Mol. Biosci.

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“…The teleost zebrafish, an increasingly popular vertebrate model for studying development and genetics, has shown promise in bringing new insights into our understanding of the ontogeny of liver macrophages and their responses to injury. Zebrafish form a functional liver by just 4 days post fertilization (6). Despite some architectural differences, the zebrafish liver contains a highly similar parenchymal and non-parenchymal cell inventory as the mammalian liver.…”

Section: Introductionmentioning

confidence: 99%

“…Despite some architectural differences, the zebrafish liver contains a highly similar parenchymal and non-parenchymal cell inventory as the mammalian liver. Taking advantages of the transparent larva and the accessibility to genetic manipulation, researchers have generated transgenic fluorescent reporter strains to mark individual liver cell types, enabling real-time tracking of their morphology and behaviors during development and injury (6). Zebrafish have been used in translational research modeling various liver diseases such as drug-induced acute liver failure, cholestasis, non-alcoholic liver disease, alcoholic liver disease, and cancer (6–8).…”

Section: Introductionmentioning

confidence: 99%

Macrophages in Zebrafish Models of Liver Diseases

2019

Self Cite

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Hepatic macrophages are key components of the liver immunity and consist of two main populations. Liver resident macrophages, known as Kupffer cells in mammals, are crucial for maintaining normal liver homeostasis. Upon injury, they become activated to release proinflammatory cytokines and chemokines and recruit a large population of inflammatory monocyte-derived macrophages to the liver. During the progression of liver diseases, macrophages are highly plastic and have opposing functions depending on the signaling cues that they receive from the microenvironment. A comprehensive understanding of liver macrophages is essential for developing therapeutic interventions that target these cells in acute and chronic liver diseases. Mouse studies have provided the bulk of our current knowledge of liver macrophages. The emergence of various liver disease models and availability of transgenic tools to visualize and manipulate macrophages have made the teleost zebrafish (Danio rerio) an attractive new vertebrate model to study liver macrophages. In this review, we summarize the origin and behaviors of macrophages in healthy and injured livers in zebrafish. We highlight the roles of macrophages in zebrafish models of alcoholic and non-alcoholic liver diseases, hepatocellular carcinoma, and liver regeneration, and how they compare with the roles that have been described in mammals. We also discuss the advantages and challenges of using zebrafish to study liver macrophages.

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“…Secondly, the hybrid human/rat WIF-B9 cell line was chosen due to its high level of differentiation into hepatocyte and its sensitivity to low concentrations of chemicals, notably alcohol 27 , 28 , compared to HepaRG cells; such a feature appears to be interesting when studying concentrations of chemicals relevant to human exposure. Finally, we focused our study on the zebrafish larva model to test in vivo our hypothesis; indeed this model is now well recognized as sharing pathophysiological processes with human, especially concerning liver diseases, with advantages of time and cost-efficiency in comparison to mammal or rodent models 29 – 31 .…”

Section: Introductionmentioning

confidence: 99%

Co-exposure to benzo[a]pyrene and ethanol induces a pathological progression of liver steatosis in vitro and in vivo

Bucher

Tête

Podechard

et al. 2018

Sci Rep

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Hepatic steatosis (i.e. lipid accumulation) and steatohepatitis have been related to diverse etiologic factors, including alcohol, obesity, environmental pollutants. However, no study has so far analyzed how these different factors might interplay regarding the progression of liver diseases. The impact of the co-exposure to the environmental carcinogen benzo[a]pyrene (B[a]P) and the lifestyle-related hepatotoxicant ethanol, was thus tested on in vitro models of steatosis (human HepaRG cell line; hybrid human/rat WIF-B9 cell line), and on an in vivo model (obese zebrafish larvae). Steatosis was induced prior to chronic treatments (14, 5 or 7 days for HepaRG, WIF-B9 or zebrafish, respectively). Toxicity and inflammation were analyzed in all models; the impact of steatosis and ethanol towards B[a]P metabolism was studied in HepaRG cells. Cytotoxicity and expression of inflammation markers upon co-exposure were increased in all steatotic models, compared to non steatotic counterparts. A change of B[a]P metabolism with a decrease in detoxification was detected in HepaRG cells under these conditions. A prior steatosis therefore enhanced the toxicity of B[a]P/ethanol co-exposure in vitro and in vivo; such a co-exposure might favor the appearance of a steatohepatitis-like state, with the development of inflammation. These deleterious effects could be partly explained by B[a]P metabolism alterations.

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Using Zebrafish to Model Liver Diseases-Where Do We Stand?

Cited by 34 publications

References 143 publications

Modeling Lysosomal Storage Diseases in the Zebrafish

Modeling Lysosomal Storage Diseases in the Zebrafish

Macrophages in Zebrafish Models of Liver Diseases

Co-exposure to benzo[a]pyrene and ethanol induces a pathological progression of liver steatosis in vitro and in vivo

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