ArticleThe Journal of clinical investigation2017
Hdac3 regulates lymphovenous and lymphatic valve formation.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- The role of the cardiac lymphatic system in heart failure "reverse remodeling": from developmental signals to druggable targets.Frontiers in immunology · 2026Review
- Mycophenolic Acid Induces Osteogenesis in Tonsil-Derived Mesenchymal Stem Cells through Inhibition of IMPDH and HDAC3.Tissue engineering and regenerative medicine · 2025Article
- Epigenetic dysregulation of energy homeostasis drives aortic valve stenosis that is treatable with metformin.JCI insight · 2025Article
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- Lymphatic System Development and Function.Current cardiology reports · 2024Review
- Congenital Vascular and Lymphatic Diseases.Circulation research · 2024Review
- ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection.Nature communications · 2024Article
- Endocardial HDAC3 is required for myocardial trabeculation.Nature communications · 2024Article
- Epigenetic determinants and non-myocardial signaling pathways contributing to heart growth and regeneration.Pharmacology & therapeutics · 2024Review
- Integrated Pathogenesis of Vascular and Cardiac Valve Disease.Circulation research · 2023Article
- Pathological MAPK activation-mediated lymphatic basement membrane disruption causes lymphangiectasia that is treatable with ravoxertinib.JCI insight · 2022Article
- Molecular Mechanisms Driving Lymphedema and Other Lymphatic Anomalies.Cold Spring Harbor perspectives in medicine · 2022Article
- Cation Channelopathies: Novel Insights into Generalized Lymphatic Dysplasia.Circulation research · 2022Article
- Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway.Circulation research · 2022Article
- Role of Transcriptional and Epigenetic Regulation in Lymphatic Endothelial Cell Development.Cells · 2022Review
- IL-1β Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum.Circulation research · 2022Article
- Cerium-Containing Bioactive Glasses Promote In Vitro Lymphangiogenesis.Pharmaceutics · 2022Article
- Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation.Frontiers in physiology · 2022Review
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Lymphedema, the most common lymphatic anomaly, involves defective lymphatic valve development; yet the epigenetic modifiers underlying lymphatic valve morphogenesis remain elusive. Here, we showed that during mouse development, the histone-modifying enzyme histone deacetylase 3 (Hdac3) regulates the formation of both lymphovenous valves, which maintain the separation of the blood and lymphatic vascular systems, and the lymphatic valves. Endothelium-specific ablation of Hdac3 in mice led to blood-filled lymphatic vessels, edema, defective lymphovenous valve morphogenesis, improper lymphatic drainage, defective lymphatic valve maturation, and complete lethality. Hdac3-deficient lymphovenous valves and lymphatic vessels exhibited reduced expression of the transcription factor Gata2 and its target genes. In response to oscillatory shear stress, the transcription factors Tal1, Gata2, and Ets1/2 physically interacted with and recruited Hdac3 to the evolutionarily conserved E-box-GATA-ETS composite element of a Gata2 intragenic enhancer. In turn, Hdac3 recruited histone acetyltransferase Ep300 to form an enhanceosome complex that promoted Gata2 expression. Together, these results identify Hdac3 as a key epigenetic modifier that maintains blood-lymph separation and integrates both extrinsic forces and intrinsic cues to regulate lymphatic valve development.
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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.