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Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation
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Journal Article
Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation
2024
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Aorta
/ Arteries
/ Embryos
/ Endothelial Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Science
/ Transient receptor potential proteins
/ Troponin
/ WNK Lysine-Deficient Protein Kinase 1 - genetics
/ WNK Lysine-Deficient Protein Kinase 1 - metabolism
/ WNK1
