LKB1 in endothelial cells is required for angiogenesis and TGFβ-mediated vascular smooth muscle cell recruitment
Copyright policy )LKB1 in endothelial cells is required for angiogenesis and TGFβ-mediated vascular smooth muscle cell recruitment
Inactivation of the tumor suppressor kinase Lkb1 in mice leads to vascular defects and midgestational lethality at embryonic day 9-11 (E9-E11). Here, we have used conditional targeting to investigate the defects underlying the Lkb1-/- phenotype. Endothelium-restricted deletion of Lkb1 led to embryonic death at E12.5 with a loss of vascular smooth muscle cells (vSMCs) and vascular disruption. Transforming growth factor beta(TGFβ) pathway activity was reduced in Lkb1-deficient endothelial cells (ECs), and TGFβ signaling from Lkb1-/- ECs to adjacent mesenchyme was defective, noted as reduced SMAD2 phosphorylation. The addition of TGFβ to mutant yolk sac explants rescued the loss of vSMCs, as evidenced by smooth muscle alpha actin(SMA) expression. These results reveal an essential function for endothelial Lkb1 in TGFβ-mediated vSMC recruitment during angiogenesis.
- University of Helsinki Finland
Male, Mice, Knockout, Myocytes, Smooth Muscle, Endothelial Cells, Gene Expression Regulation, Developmental, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Embryo, Mammalian, Muscle, Smooth, Vascular, Enzyme Activation, Tissue Culture Techniques, Transforming Growth Factor beta1, Mice, Animals, Female, Endothelium, Signal Transduction
Male, Mice, Knockout, Myocytes, Smooth Muscle, Endothelial Cells, Gene Expression Regulation, Developmental, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Embryo, Mammalian, Muscle, Smooth, Vascular, Enzyme Activation, Tissue Culture Techniques, Transforming Growth Factor beta1, Mice, Animals, Female, Endothelium, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).40 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!