PUBLICATION

Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation

Authors
Bowley, G., Irving, S., Hoefer, I., Wilkinson, R., Pasterkamp, G., Darwish, H.M.S., White, S., Francis, S.E., Chico, T., Noel, E., Serbanovic-Canic, J., Evans, P.C.
ID
ZDB-PUB-241204-5
Date
2024
Source
Scientific Reports   14: 3013030130 (Journal)
Registered Authors
Chico, Tim J., Noël, Emily, Serbanovic-Canic, Jovana, Wilkinson, Robert
Keywords
Endothelial cells, Proliferation, Shear stress, WNK1
MeSH Terms
  • WNK Lysine-Deficient Protein Kinase 1/genetics
  • WNK Lysine-Deficient Protein Kinase 1/metabolism
  • Animals
  • Stress, Mechanical
  • Mice
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Endothelial Cells*/metabolism
  • Zebrafish*/genetics
  • Cell Proliferation*
  • Humans
(all 11)
PubMed
39627337 Full text @ Sci. Rep.
Abstract
Local haemodynamics control arterial homeostasis and dysfunction by generating wall shear stress (WSS) which regulates endothelial cell (EC) physiology. Here we use a zebrafish model to identify genes that regulate EC proliferation in response to flow. Suppression of blood flow in zebrafish embryos (by targeting cardiac troponin) reduced EC proliferation in the intersegmental vessels (ISVs) compared to controls exposed to flow. The expression of candidate regulators of proliferation was analysed in EC isolated from zebrafish embryos by qRT-PCR. Genes shown to be expressed in EC were analysed for the ability to regulate proliferation in zebrafish vasculature exposed to flow or no-flow conditions using a knockdown approach. wnk1 negatively regulated proliferation in no-flow conditions, whereas fzd5, gsk3β, trpm7 and bmp2a promoted proliferation in EC exposed to flow. Immunofluorescent staining of mammalian arteries revealed that WNK1 is expressed at sites of low WSS in the murine aorta, and in EC overlying human atherosclerotic plaques. We conclude that WNK1 is expressed in EC at sites of low WSS and in diseased arteries and may influence vascular homeostasis by reducing EC proliferation.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Bowley, G., Irving, S., Hoefer, I., Wilkinson, R., Pasterkamp, G., Darwish, H.M.S., White, S., Francis, S.E., Chico, T., Noel, E., Serbanovic-Canic, J., Evans, P.C. (2024) Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation. Scientific Reports. 14:3013030130.