RRC ID 51255
Author Wu J, Choi TY, Shin D.
Title tomm22 Knockdown-Mediated Hepatocyte Damages Elicit Both the Formation of Hybrid Hepatocytes and Biliary Conversion to Hepatocytes in Zebrafish Larvae.
Journal Gene Expr
Abstract The liver has a highly regenerative capacity. In the normal liver, hepatocytes proliferate to restore lost liver mass. However, when hepatocyte proliferation is impaired, biliary epithelial cells (BECs) activate and contribute to hepatocytes. We previously reported in zebrafish that upon severe hepatocyte ablation, BECs extensively contribute to regenerated hepatocytes. It was also speculated that BEC-driven liver regeneration might occur in another zebrafish liver injury model in which temporary knockdown of the mitochondrial import gene tomm22 by morpholino antisense oligonucleotides (MO) induces hepatocyte death. Given the importance of multiple BEC-driven liver regeneration models for better elucidating the mechanisms underlying innate liver regeneration in the diseased liver, we hypothesized that BECs would contribute to hepatocytes in tomm22 MO-injected larvae. In this MO-based liver injury model, by tracing the lineage of BECs, we found that BECs significantly contributed to hepatocytes. Moreover, we found that surviving, preexisting hepatocytes become BEC-hepatocyte hybrid cells in tomm22 MO-injected larvae. Intriguingly, both the inhibition of Wnt/β-catenin signaling and macrophage ablation suppressed the formation of the hybrid hepatocytes. This new liver injury model in which both hepatocytes and BECs contribute to regenerated hepatocytes will aid in better understanding the mechanisms of innate liver regeneration in the diseased liver.
Volume 17(3)
Pages 237-249
Published 2017-7-7
DOI 10.3727/105221617X695195
PMID 28251883
PMC PMC5542045
MeSH Animals Animals, Genetically Modified Biliary Tract / metabolism* Cell Death Cell Proliferation Gene Knockdown Techniques Green Fluorescent Proteins / metabolism Hepatocytes / cytology* Larva Liver / injuries Liver / pathology Liver / physiology* Liver Regeneration* Macrophages / cytology Mitochondrial Membrane Transport Proteins / genetics* Mitochondrial Precursor Protein Import Complex Proteins Models, Animal Oligonucleotides, Antisense / genetics Organ Size Signal Transduction Wnt Proteins / metabolism Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / genetics* beta Catenin / metabolism
Zebrafish Tg(6xTcf/LefBS-miniP:d2EGFP)