ArticleBlood2010
Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 211 citations in OpenAlex.
- Fluid Forces Control Structural Remodeling of Blind-Ended Lymphatic Microvessels.Advanced healthcare materials · 2026Article
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- NF-κB-driven lymphangiogenesis affects kidney function via a VEGFR-3-mediated pathway.JCI insight · 2026Article
- Lysophosphatidic acid-mediated NF-κB activation promotes FOXC2 expression essential for lymphatic valve development.The Journal of clinical investigation · 2026Article
- Mechanobiological modulation: physiological pressure preconditioning boosts the paracrine-driven lymphangiogenic capacity of bone marrow mesenchymal stem cells.Frontiers in physiology · 2026Article
- From defense to disease: the multifaceted role of lymphatics during infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- IL-19 Is a Novel Lymphangiocrine Factor Inducing Lymphangiogenesis and Lymphatic Junctional Regulation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- RIPK3-Mediated Necroptosis Drives Macrophage Infiltration and Corneal Neovascularization After Alkali Burn.Investigative ophthalmology & visual science · 2025Article
- Dual role of vascular endothelial growth factor-C in post-stroke recovery.The Journal of experimental medicine · 2025Article
- Lymphatic-immune interactions in the musculoskeletal system.Frontiers in immunology · 2025Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Article
- Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation.Development (Cambridge, England) · 2024Article
- Tumour vasculature at single-cell resolution.Nature · 2024Article
- Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review.World journal of hepatology · 2024Review
- Alkali injury-induced pathological lymphangiogenesis in the iris facilitates the infiltration of T cells and ocular inflammation.JCI insight · 2024Article
- Repositioning the Early Pathology of Type 1 Diabetes to the Extraislet Vasculature.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Construction and applications of the EOMA spheroid model of Kaposiform hemangioendothelioma.Journal of biological engineering · 2024Article
- Crohn's disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data.World journal of gastroenterology · 2024Review
- Inhibition of Lymphangiogenesis: A Protective Role of microRNA 146a-5p in Breast Cancer.The breast journal · 2024Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
The concept of inflammation-induced lymphangiogenesis (ie, formation of new lymphatic vessels) has long been recognized, but the molecular mechanisms remained largely unknown. The 2 primary mediators of lymphangiogenesis are vascular endothelial growth factor receptor-3 (VEGFR-3) and Prox1. The key factors that regulate inflammation-induced transcription are members of the nuclear factor-kappaB (NF-kappaB) family; however, the role of NF-kappaB in regulation of lymphatic-specific genes has not been defined. Here, we identified VEGFR-3 and Prox1 as downstream targets of the NF-kappaB pathway. In vivo time-course analysis of inflammation-induced lymphangiogenesis showed activation of NF-kappaB followed by sequential up-regulation of Prox1 and VEGFR-3 that preceded lymphangiogenesis by 4 and 2 days, respectively. Activation of NF-kappaB by inflammatory stimuli also elevated Prox1 and VEGFR-3 expression in cultured lymphatic endothelial cells, resulting in increased proliferation and migration. We also show that Prox1 synergizes with the p50 of NF-kappaB to control VEGFR-3 expression. Collectively, our findings suggest that induction of the NF-kappaB pathway by inflammatory stimuli activates Prox1, and both NF-kappaB and Prox1 activate the VEGFR-3 promoter leading to increased receptor expression in lymphatic endothelial cells. This, in turn, enhances the responsiveness of preexisting lymphatic endothelium to VEGFR-3 binding factors, VEGF-C and VEGF-D, ultimately resulting in robust lymphangiogenesis.
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