Essential role of apelin signaling during lymphatic development in zebrafish
- Authors
- Kim, J.D., Kang, Y., Kim, J., Papangeli, I., Kang, H., Wu, J., Park, H., Nadelmann, E., Rockson, S.G., Chun, H.J., and Jin, S.W.
- ID
- ZDB-PUB-140127-22
- Date
- 2014
- Source
- Arterioscler. Thromb. Vasc. Biol. 34(2): 338-345 (Journal)
- Registered Authors
- Jin, Suk-Won, Kim, Jun-Dae
- Keywords
- APJ receptor, apelin protein, lymphatic vessels, zebrafish
- MeSH Terms
-
- Animals
- Cells, Cultured
- Chemokines/genetics
- Chemokines/metabolism*
- Endothelial Cells/metabolism
- Endothelium, Lymphatic/embryology
- Endothelium, Lymphatic/metabolism
- Humans
- Intercellular Signaling Peptides and Proteins/metabolism
- Lymphangiogenesis*
- Mitogen-Activated Protein Kinase 1/metabolism
- Mitogen-Activated Protein Kinase 3/metabolism
- Phosphorylation
- Proto-Oncogene Proteins c-akt/metabolism
- RNA Interference
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism
- Signal Transduction*
- Thoracic Duct/embryology
- Thoracic Duct/metabolism*
- Time Factors
- Transfection
- Vascular Endothelial Growth Factor C/metabolism
- Vascular Endothelial Growth Factor Receptor-3/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 24311379 Full text @ Arterioscler. Thromb. Vasc. Biol.
Approach and Results—We investigated the functions of Apelin signaling during lymphatic development using zebrafish embryos and found that attenuation of Apelin signaling substantially decreased the formation of the parachordal vessel and the number of lymphatic endothelial cells within the developing thoracic duct, indicating an essential role of Apelin signaling during the early phase of lymphatic development. Mechanistically, we found that abrogation of Apelin signaling selectively attenuates lymphatic endothelial serine–threonine kinase Akt 1/2 phosphorylation without affecting the phosphorylation status of extracellular signal–regulated kinase 1/2. Moreover, lymphatic abnormalities caused by the reduction of Apelin signaling were significantly exacerbated by the concomitant partial inhibition of serine–threonine kinase Akt/protein kinase B signaling. Apelin and vascular endothelial growth factor-C (VEGF-C) signaling provide a nonredundant activation of serine–threonine kinase Akt/protein kinase B during lymphatic development because overexpression of VEGF-C or apelin was unable to rescue the lymphatic defects caused by the lack of Apelin or VEGF-C, respectively.
Conclusions—Taken together, our data present compelling evidence suggesting that Apelin signaling regulates lymphatic development by promoting serine–threonine kinase Akt/protein kinase B activity in a VEGF-C/VEGF receptor 3–independent manner during zebrafish embryogenesis.