ArticleThe Journal of clinical investigation2022
Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 98 citations in OpenAlex.
- Cardiac lymphatic dysfunction and repair in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Review
- Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels.Nature neuroscience · 2026Article
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- RAS-PI3Kα signaling regulates KrasG12D-induced lymphangiogenesis in complex lymphatic anomalies.Disease models & mechanisms · 2026Article
- Endothelial VEGFR2 insufficiency promotes the transition of lymphatic to hematopoietic transcriptional programs.Angiogenesis · 2026Article
- SETD2 Improves Endothelial Function and Angiogenesis in Diabetic Hindlimb Ischemia Via Activating ANGPT2-PI3K/AKT Pathway.Cardiovascular toxicology · 2026Article
- A Biomimetic Nanoparticle System Intercepts and Degrades Thrombospondin-1 to Restore Vascular Homeostasis After Ischemic Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- VEGFC as a prognostic cytokine biomarker linking lymph node metastasis to immune suppression in breast cancer.European cytokine network · 2026Article
- Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling.The Journal of clinical investigation · 2026Article
- [Research progress on vascular endothelial growth factor C in meningeal lymphatic vessel-mediated clearance of amyloid β-protein].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- VEGFR2 is required for VEGF-C-VEGFR3-PI3Kα-mediated sprouting lymphangiogenesis.Nature communications · 2026Article
- Tumor Anti-Angiogenesis Therapy and Its Influence on Immune Cell Function in the Tumor Microenvironment.Cancer medicine · 2026Review
- Ionic Extracts of Magnesium Powders Promote In Vitro Lymphangiogenesis.Biomedicines · 2026Article
- Application value of gastric contrast ultrasonography in gastric tumors.Insights into imaging · 2026Review
- Pancreatic Lymphatics in Health and Disease: Evolution, Embryology, and Neural Control.Lymphatics · 2026Article
- Shuxuening injection improves ventricular remodeling after myocardial infarction by indirectly promoting macrophage-mediated angiogenesis and lymphangiogenesis.Chinese medicine · 2026Article
- Immune remodeling of tumor-draining lymph nodes: mechanistic determinants of checkpoint blockade responsiveness.Frontiers in immunology · 2026Review
- Effects of vascular endothelial growth factor-A and -C on wound healing in wild-type mice.PloS one · 2026Article
- Mechanistic study of Shenge powder on myocardial hypertrophy and cardiac lymphatic intervention in TAC-induced mouse models.Frontiers in pharmacology · 2026Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C-induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110α subunit or with small-molecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C-induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling.
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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.