Bowley, G., Irving, S., Hoefer, I. et al. (9 more authors) (2024) Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation. Scientific Reports, 14 (1). 30130. ISSN 2045-2322
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | Endothelial cells; Proliferation; Shear stress; WNK1; Animals; Zebrafish; Cell Proliferation; Endothelial Cells; Humans; Zebrafish Proteins; Mice; Stress, Mechanical; WNK Lysine-Deficient Protein Kinase 1 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number National Centre for the Replacement Refinement and Reduction of Animals in Research NC/R001618/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Dec 2024 09:31 |
Last Modified: | 12 Dec 2024 09:31 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s41598-024-77370-1 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:220617 |