PUBLICATION
Blood Flow Regulates Zebrafish Caudal Vein Plexus Angiogenesis by ERK5-klf2a-nos2b Signaling
- Authors
- Xie, X., Zhou, T., Wang, Y., Chen, H., Lei, D., Huang, L., Wang, Y., Jin, X., Sun, T., Tan, J., Yin, T., Huang, J., Gregersen, H., Wang, G.
- ID
- ZDB-PUB-180327-14
- Date
- 2018
- Source
- Current Molecular Medicine 18(1): 3-14 (Journal)
- Registered Authors
- Huang, Lu, Jin, Xuepu, Lei, Daoxi, Wang, Guixue, Wang, Yeqi, Wang, Yi
- Keywords
- none
- MeSH Terms
-
- Animals
- Blood Flow Velocity/physiology
- Embryo, Nonmammalian/embryology
- Kruppel-Like Transcription Factors/genetics
- Kruppel-Like Transcription Factors/metabolism*
- MAP Kinase Signaling System/physiology*
- Mitogen-Activated Protein Kinase 7/genetics
- Mitogen-Activated Protein Kinase 7/metabolism*
- Neovascularization, Physiologic/physiology*
- Nitric Oxide Synthase Type II/genetics
- Nitric Oxide Synthase Type II/metabolism*
- Veins/embryology*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 29577856 Full text @ Curr. Mol. Med.
Citation
Xie, X., Zhou, T., Wang, Y., Chen, H., Lei, D., Huang, L., Wang, Y., Jin, X., Sun, T., Tan, J., Yin, T., Huang, J., Gregersen, H., Wang, G. (2018) Blood Flow Regulates Zebrafish Caudal Vein Plexus Angiogenesis by ERK5-klf2a-nos2b Signaling. Current Molecular Medicine. 18(1):3-14.
Abstract
Vascular network formation induced by angiogenesis plays an important role in many physiological and pathological processes. However, the role of blood flow and underlying mechanisms in vascular network formation, for example for the development of the caudal vein plexus (CVP), is poorly understood. In this study on tnnt2a-MO injection and chemical blood flow modulator treatment in zebrafish embryos, we demonstrated that decreased blood flow disrupted CVP formation. The hemodynamic force was quantitatively analyzed. Furthermore, CVP angiogenesis in zebrafish embryos was inhibited by disruption of the blood flow downstream effectors ERK5, klf2a, and nos2b in response to treatment with the ERK5 specific inhibitor and to injection of klf2a-MO, nos2b-MO. Overexpression of klf2a mRNA or nos2b mRNA restored vascular defects in tnnt2a or klf2a morphants. The data suggest that flow-induced ERK5-klf2a-nos2b signaling is involved in CVP angiogenesis in zebrafish embryos. In conclusion, we have demonstrated that blood flow is essential for vascular network formation, specifically for CVP angiogenesis in zebrafish. A novel genetic and mechanical mechanism was discovered in which ERK5 facilitates the integration of blood flow with the downstream klf2a-nos2b signaling for CVP angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping