ArticleThe Journal of experimental medicine2017
Human venous valve disease caused by mutations in FOXC2 and GJC2.
Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 34 citations in OpenAlex.
- FOXC2 represses NFAT1-dependent transcription through a DNA-facilitated protein-protein interaction.Nucleic acids research · 2026Article
- Review
- Progress of the pathogenesis in varicocele: a narrative review.The Canadian journal of urology · 2026Review
- Downregulation of serum Foxc2 in dilated cardiomyopathy: association with disease severity and cardiac function.Future science OA · 2025Article
- Suppression of 6-pyruvoyl-tetrahydropterin synthase promotes remyelination in multiple sclerosis.BMC medicine · 2025Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- Endovenous thermal ablation of superficial truncal veins and compression therapy result in symptom relief in venous valve aplasia.Journal of vascular surgery cases and innovative techniques · 2023Article
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Mutations in EPHB4 cause human venous valve aplasia.JCI insight · 2021Article
- Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management.Journal of clinical medicine · 2021Review
- Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels.The EMBO journal · 2021Article
- Lymphatic Connexins and Pannexins in Health and Disease.International journal of molecular sciences · 2021Review
- The Lymphatic Vasculature in the 21Cell · 2020Review
- Hemodynamic regulation of perivalvular endothelial gene expression prevents deep venous thrombosis.The Journal of clinical investigation · 2019Article
- Endothelial connexins in vascular function.Vascular biology (Bristol, England) · 2019Review
- Mechanisms of Connexin-Related Lymphedema.Circulation research · 2018Article
- Connexins and Pannexins in Vascular Function and Disease.International journal of molecular sciences · 2018Review
- Implication of the PI3K/Akt/mTOR Pathway in the Process of Incompetent Valves in Patients with Chronic Venous Insufficiency and the Relationship with Aging.Oxidative medicine and cellular longevity · 2018Article
- Intraluminal valves: development, function and disease.Disease models & mechanisms · 2017Review
- Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function.PloS one · 2017Article
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 4 countries.
Funding
Abstract
Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1hi endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1hi endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events. Genetic deletion of Gjc2, Gja4, or Gja1 also disrupted early VV Prox1hi endothelial organization at postnatal day 0, and this likely underlies the VV defects seen in patients with GJC2 mutations. Knockout of Gja4 or Gjc2 resulted in reduced proliferation of Prox1hi valve-forming cells. At later stages of blood flow, Foxc2 and calcineurin-Nfat signaling are each required for growth of the valve leaflets, whereas Foxc2 is not required for VV maintenance.
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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.