Endothelial Cell SMAD6 Balances ACVRL1/Alk1 Function to Regulate Adherens Junctions and Hepatic Vascular Development.

ABSTRACT: BMP signaling is critical to blood vessel formation and function, but how pathway components regulate vascular development is not well-understood. Here we find that inhibitory SMAD6 functions in endothelial cells to negatively regulate ALK1/ACVRL1-mediated responses, and it is required to prevent vessel dysmorphogenesis and hemorrhage in the embryonic liver vasculature. Reduced Alk1 gene dosage rescued embryonic hepatic hemorrhage and microvascular capillarization induced by Smad6 deletion in endothelial cells in vivo . At the cellular level, co-depletion of Smad6 and Alk1 rescued the destabilized junctions and impaired barrier function of endothelial cells depleted for SMAD6 alone. At the mechanistic level, blockade of actomyosin contractility or increased PI3K signal

SUBMITTER: Kulikauskas MR 

PROVIDER: S-EPMC10055411 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature