ArticleThe Journal of clinical investigation2015
Lymph flow regulates collecting lymphatic vessel maturation in vivo.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 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
107 citing papers in PubMed, 169 citations in OpenAlex.
- Central nervous system lymphatic network: from the maintenance of brain homeostasis to emerging therapeutic perspectives in neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- CXCL12/CXCR4 Governs Lymphatic Valve Formation Through Flow Dependent AKT/FOXO1/FOXC2 Activation.bioRxiv : the preprint server for biology · 2026Article
- Mechanoreceptor plexin D1 regulates lymphatic valve morphogenesis and lymphedema pathogenesis.The Journal of clinical investigation · 2026Article
- A Versatile Microfluidic Extrusion-Based Hydrogel Platform for Self-Organization and Long-Term Maintenance of Engineered 3D Lymphatic Endothelium.Advanced healthcare materials · 2026Article
- Lysophosphatidic acid-mediated NF-κB activation promotes FOXC2 expression essential for lymphatic valve development.The Journal of clinical investigation · 2026Article
- New Strategies for the Prevention and Therapy of Alzheimer's Disease Based on Stimulation of Brain Drainage and Lymphatic Clearance.International journal of molecular sciences · 2026Review
- Neuro-lymphaphotonics opens new horizons of the future technologies for the therapy of brain diseases.Theranostics · 2026Review
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- Sleep is a therapeutic window for photostimulation of drainage of aging brain.Frontiers of optoelectronics · 2025Article
- S1PR1 regulates lymphatic valve development and tertiary lymphoid organ formation in the ileum.The Journal of experimental medicine · 2025Article
- TIE1-dependent lymphatic vascular remodeling is mediated by its second tyrosine kinase domain.Development (Cambridge, England) · 2025Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- Understanding the Lymphatic System: Tissue-on-Chip Modeling.Annual review of biomedical engineering · 2025Review
- Age as a limiting factor for effectiveness of photostimulation of brain drainage and cognitive functions.Frontiers of optoelectronics · 2025Article
- Mice with lymphatic dysfunction develop pathogenic lung tertiary lymphoid organs that model an autoimmune emphysema phenotype of COPD.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Lymphatic System Development and Function.Current cardiology reports · 2024Review
- Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases.Journal of biomedical research · 2024Article
- Lung lymphatic endothelial cells undergo inflammatory and prothrombotic changes in a model of chronic obstructive pulmonary disease.Frontiers in cell and developmental biology · 2024Article
- Response of lymphatic endothelial cells to combined spatial and temporal variations in fluid flow.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Fluid shear forces have established roles in blood vascular development and function, but whether such forces similarly influence the low-flow lymphatic system is unknown. It has been difficult to test the contribution of fluid forces in vivo because mechanical or genetic perturbations that alter flow often have direct effects on vessel growth. Here, we investigated the functional role of flow in lymphatic vessel development using mice deficient for the platelet-specific receptor C-type lectin-like receptor 2 (CLEC2) as blood backfills the lymphatic network and blocks lymph flow in these animals. CLEC2-deficient animals exhibited normal growth of the primary mesenteric lymphatic plexus but failed to form valves in these vessels or remodel them into a structured, hierarchical network. Smooth muscle cell coverage (SMC coverage) of CLEC2-deficient lymphatic vessels was both premature and excessive, a phenotype identical to that observed with loss of the lymphatic endothelial transcription factor FOXC2. In vitro evaluation of lymphatic endothelial cells (LECs) revealed that low, reversing shear stress is sufficient to induce expression of genes required for lymphatic valve development and identified GATA2 as an upstream transcriptional regulator of FOXC2 and the lymphatic valve genetic program. These studies reveal that lymph flow initiates and regulates many of the key steps in collecting lymphatic vessel maturation and 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.