ArticleThe Journal of clinical investigation2016
CHD4-regulated plasmin activation impacts lymphovenous hemostasis and hepatic vascular integrity.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 33 citations in OpenAlex.
- Plasmin and sterile inflammation jointly drive fatal embryonic liver degeneration in endothelial chromatin remodeler mutant mice.Development (Cambridge, England) · 2026Article
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- Endothelial Chromatin-Remodeling Enzymes Regulate the Production of Critical ECM Components During Murine Lung Development.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Increased Matrix Metalloproteinase-1 Activation Enhances Disruption and Regression of k-RasV12-Expressing Arteriovenous Malformation-Like Vessels.The American journal of pathology · 2023Article
- Generation of a Well-Characterized Homozygous Chromodomain-Helicase-DNA-Binding Protein 4International journal of molecular sciences · 2023Article
- 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
- Fetal nuchal edema and developmental anomalies caused by gene mutations in mice.Frontiers in cell and developmental biology · 2022Review
- Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation.Frontiers in physiology · 2022Review
- Biochemical and mechanical signals in the lymphatic vasculature.Cellular and molecular life sciences : CMLS · 2021Review
- The NuRD chromatin-remodeling complex enzyme CHD4 prevents hypoxia-induced endothelial Ripk3 transcription and murine embryonic vascular rupture.Cell death and differentiation · 2020Article
- Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function.Cell death & disease · 2020Article
- The chromatin-remodeling enzyme CHD3 plays a role in embryonic viability but is dispensable for early vascular development.PloS one · 2020Article
- Establishment and maintenance of blood-lymph separation.Cellular and molecular life sciences : CMLS · 2019Review
- Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Excessive Plasmin Compromises Hepatic Sinusoidal Vascular Integrity After Acetaminophen Overdose.Hepatology (Baltimore, Md.) · 2018Article
- Hdac3 regulates lymphovenous and lymphatic valve formation.The Journal of clinical investigation · 2017Article
- Lymphatic Endothelial Cell Plasticity in Development and Disease.Physiology (Bethesda, Md.) · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The chromatin-remodeling enzyme CHD4 maintains vascular integrity at mid-gestation; however, it is unknown whether this enzyme contributes to later blood vessel or lymphatic vessel development. Here, we addressed this issue in mice harboring a deletion of Chd4 specifically in cells that express lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), which include lymphatic endothelial cells (LECs) and liver sinusoidal endothelial cells. Chd4 mutant embryos died before birth and exhibited severe edema, blood-filled lymphatics, and liver hemorrhage. CHD4-deficient embryos developed normal lymphovenous (LV) valves, which regulate the return of lymph to the blood circulation; however, these valves lacked the fibrin-rich thrombi that prevent blood from entering the lymphatic system. Transcripts of the urokinase plasminogen activator receptor (uPAR), which facilitates activation of the fibrin-degrading protease plasmin, were upregulated in Chd4 mutant LYVE1+ cells, and plasmin activity was elevated near the LV valves. Genetic reduction of the uPAR ligand urokinase prevented degradation of fibrin-rich thrombi at the LV valves and largely resolved the blood-filled lymphatics in Chd4 mutants. Urokinase reduction also ameliorated liver hemorrhage and prolonged embryonic survival by reducing plasmin-mediated extracellular matrix degradation around sinusoidal blood vessels. These results highlight the susceptibility of LV thrombi and liver sinusoidal vessels to plasmin-mediated damage and demonstrate the importance of CHD4 in regulating embryonic plasmin activation after mid-gestation.
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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.