ArticleDevelopmental biology2018
Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted endothelial cell junctions.
Article in Developmental biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
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- Smad3 deficiency attenuates disease severity in a zebrafish model for Smad6-related aortic disease.Angiogenesis · 2026Article
- Ectopic Expansion of Pulmonary Vasculature in Fibrotic Lung Disease and Lung Adenocarcinoma Marked by Proangiogenic COL15A1+ Endothelial Cells.Pulmonary circulation · 2025Article
- Plakoglobin does not participate in endothelial barrier stabilization mediated by cAMP.Scientific reports · 2025Article
- Single-cell analysis reveals the loss of FABP4-positive proliferating valvular endothelial cells relates to functional mitral regurgitation.BMC medicine · 2024Article
- HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death.International journal of molecular sciences · 2024Article
- Endothelial cell SMAD6 balances Alk1 function to regulate adherens junctions and hepatic vascular development.Development (Cambridge, England) · 2023Article
- Nuclear SUN1 stabilizes endothelial cell junctions via microtubules to regulate blood vessel formation.eLife · 2023Article
- Endothelial Cell SMAD6 Balances ACVRL1/Alk1 Function to Regulate Adherens Junctions and Hepatic Vascular Development.bioRxiv : the preprint server for biology · 2023Article
- SMAD6-deficiency in human genetic disorders.NPJ genomic medicine · 2022Review
- Analyzing siRNA Concentration, Complexation and Stability in Cationic Dendriplexes by Stem-Loop Reverse Transcription-qPCR.Pharmaceutics · 2022Article
- Neuropilin-1 deficiency in vascular smooth muscle cells is associated with hereditary hemorrhagic telangiectasia arteriovenous malformations.JCI insight · 2022Article
- The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function.Cellular and molecular life sciences : CMLS · 2022Review
- Association of TGF-β Canonical Signaling-Related Core Genes With Aortic Aneurysms and Aortic Dissections.Frontiers in pharmacology · 2022Review
- Parallels between the Developing Vascular and Neural Systems: Signaling Pathways and Future Perspectives for Regenerative Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology.International journal of molecular sciences · 2021Review
- SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis.Angiogenesis · 2021Article
- Bone Morphogenetic Proteins and Diabetic Retinopathy.Biomolecules · 2021Review
- A Multi-Omics Approach Using a Mouse Model of Cardiac Malformations for Prioritization of Human Congenital Heart Disease Contributing Genes.Frontiers in cardiovascular medicine · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The BMP pathway regulates developmental processes including angiogenesis, yet its signaling outputs are complex and context-dependent. Recently, we showed that SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases vessel sprouting and branching both in vitro and in zebrafish. Genetic deletion of SMAD6 in mice results in poorly characterized cardiovascular defects and lethality. Here, we analyzed the effects of SMAD6 loss on vascular function during murine development. SMAD6 was expressed in a subset of blood vessels throughout development, primarily in arteries, while expression outside of the vasculature was largely confined to developing cardiac valves with no obvious embryonic phenotype. Mice deficient in SMAD6 died during late gestation and early stages of postnatal development, and this lethality was associated with vessel hemorrhage. Mice that survived past birth had increased branching and sprouting of developing postnatal retinal vessels and disorganized tight and adherens junctions. In vitro, knockdown of SMAD6 led to abnormal endothelial cell adherens junctions and increased VE-cadherin endocytosis, indicative of activated endothelium. Thus, SMAD6 is essential for proper blood vessel function during murine development, where it appears to stabilize endothelial junctions to prevent hemorrhage and aberrant angiogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.