ArticleAmerican journal of physiology. Cell physiology2012
Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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.
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Who cites it
54 citing papers in PubMed, 79 citations in OpenAlex.
- Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema.JCI insight · 2018Trial
- Cardiac lymphatic dysfunction and repair in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Bidirectional crosstalk between obesity and the lymphatic system: a novel pathway in obesity pathogenesis and treatment.International journal of obesity (2005) · 2026Review
- A perforator-based adipocutaneous skin paddle derived from free muscle flap reconstruction as a hypothesis-generating human tissue model of early localized lymphatic insufficiency.Scientific reports · 2026Article
- Tamoxifen attenuates postsurgical hindlimb swelling and soft-tissue fibrosis in a rat model of secondary lymphatic injury.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- TGF-β-mediated epithelial-mesenchymal transition of keratinocytes promotes fibrosis in secondary lymphedema.JCI insight · 2025Article
- Dysregulated lymphatic remodeling promotes immunopathology during non-healing cutaneous leishmaniasis.bioRxiv : the preprint server for biology · 2025Article
- Increased Microvascular Filtration and Vascular Endothelial Growth Factor-D associated with Changed Lymphatic Vessel Morphology in Breast Cancer Treated Patients.Plastic and reconstructive surgery. Global open · 2024Article
- Review
- Article
- The emerging importance of lymphatics in health and disease: an NIH workshop report.The Journal of clinical investigation · 2023Review
- Topical captopril: a promising treatment for secondary lymphedema.Translational research : the journal of laboratory and clinical medicine · 2023Article
- Cystathionine β-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3.Communications biology · 2022Article
- Current Understanding of Pathological Mechanisms of Lymphedema.Advances in wound care · 2022Review
- TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation.Clinical and translational medicine · 2022Article
- Interferon-γ: teammate or opponent in the tumour microenvironment?Nature reviews. Immunology · 2022Review
- Crosstalk Between Adipose and Lymphatics in Health and Disease.Endocrinology · 2022Review
- Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity.Metabolites · 2021Review
- Follicular regulatory helper T cells control the response of regulatory B cells to a high-cholesterol diet.Cardiovascular research · 2021Article
- T-cells produce acidic niches in lymph nodes to suppress their own effector functions.Nature communications · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Lymphangiogenic cytokines such as vascular endothelial growth factor-C (VEGF-C) are critically required for lymphatic regeneration; however, in some circumstances, lymphatic function is impaired despite normal or elevated levels of these cytokines. The recent identification of anti-lymphangiogenic molecules such as interferon-γ (IFN-γ), transforming growth factor-β1, and endostatin has led us to hypothesize that impaired lymphatic function may represent a dysregulated balance in the expression of pro/anti-lymphangiogenic stimuli. We observed that nude mice have significantly improved lymphatic function compared with wild-type mice in a tail model of lymphedema. We show that gradients of lymphatic fluid stasis regulate the expression of lymphangiogenic cytokines (VEGF-A, VEGF-C, and hepatocyte growth factor) and that paradoxically the expression of these molecules is increased in wild-type mice. More importantly, we show that as a consequence of T-cell-mediated inflammation, these same gradients also regulate expression patterns of anti-lymphangiogenic molecules corresponding temporally and spatially with impaired lymphatic function in wild-type mice. We show that neutralization of IFN-γ significantly increases inflammatory lymph node lymphangiogenesis independently of changes in VEGF-A or VEGF-C expression, suggesting that alterations in the balance of pro- and anti-lymphangiogenic cytokine expression can regulate lymphatic vessel formation. In conclusion, we show that gradients of lymphatic fluid stasis regulate not only the expression of pro-lymphangiogenic cytokines but also potent suppressors of lymphangiogenesis as a consequence of T-cell inflammation and that modulation of the balance between these stimuli can regulate lymphatic function.
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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.