PUBLICATION
Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in zebrafish
- Authors
- Lee, S.H., So, J.H., Kim, H.T., Choi, J.H., Lee, M.S., Choi, S.Y., Kim, C.H., Kim, M.J.
- ID
- ZDB-PUB-140513-244
- Date
- 2014
- Source
- Biochemical and Biophysical Research Communications 446: 1237-42 (Journal)
- Registered Authors
- So, Juhoon
- Keywords
- Angiogenesis, Angiopoietin-like 3, Angptl3, Hypobetalipoproteinemia, Liver, Zebrafish
- MeSH Terms
-
- Angiopoietins/genetics
- Angiopoietins/metabolism*
- Animals
- Cell Proliferation*
- Gene Expression
- Gene Expression Regulation, Developmental
- Gene Knockdown Techniques
- Hepatocytes/cytology*
- Hepatocytes/metabolism
- Hypobetalipoproteinemias/genetics
- Hypobetalipoproteinemias/metabolism
- Lipid Metabolism*
- Liver/anatomy & histology
- Liver/embryology*
- Liver/metabolism
- Organ Size
- Zebrafish/anatomy & histology
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 24685482 Full text @ Biochem. Biophys. Res. Commun.
Citation
Lee, S.H., So, J.H., Kim, H.T., Choi, J.H., Lee, M.S., Choi, S.Y., Kim, C.H., Kim, M.J. (2014) Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in zebrafish. Biochemical and Biophysical Research Communications. 446:1237-42.
Abstract
Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) cause familial hypobetalipoproteinemia type 2 (FHBL2) in humans. ANGPTL3 belongs to the angiopoietin-like family, the vascular endothelial growth factor family that is structurally similar to angiopoietins and is known for a regulator of lipid and glucose metabolism, although it is unclear how mutations in ANGPTL3 lead to defect in liver development in the vertebrates. We report here that angptl3 is primarily expressed in the zebrafish developing liver and that morpholino (MO) knockdown of Angptl3 reduces the size of the developing liver, which is caused by suppression of cell proliferation, but not by enhancement of apoptosis. However, MO knockdown of Angptl3 did not alter angiogenesis in the developing liver. Additionally, disruption of zebrafish Angptl3 elicits the hypocholesterolemia phenotype that is characteristic of FHBL2 in humans. Together, our findings propose a novel role for Angptl3 in liver cell proliferation and maintenance during zebrafish embryogenesis. Finally, angptl3 morphants will serve as a good model for understanding the pathophysiology of FHBL2.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping