WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis.

ABSTRACT: Angiogenesis is essential for growth of new blood vessels, remodeling existing vessels, and repair of damaged vessels, and these require reorganization of endothelial cell-cell junctions through a partial endothelial-mesenchymal transition. Homozygous disruption of the gene encoding the protein kinase WNK1 results in lethality in mice near embryonic day (E) 12 due to impaired angiogenesis. This angiogenesis defect can be rescued by endothelial-specific expression of an activated form of the WNK1 substrate kinase OSR1. We show that inhibition of WNK1 kinase activity not only prevents sprouting of endothelial cells from aortic slices but also vessel extension in inhibitor-treated embryos ex vivo. Mutations affecting TGF-β signaling also result in abnormal vascular development beginning by E1

SUBMITTER: Jaykumar AB 

PROVIDER: S-EPMC9335306 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature