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Human VEGF-D

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Function

Vascular Endothelial Growth Factor D (VEGF-D) is a secreted glycoprotein belonging to the platelet-derived growth factor (PDGF)/VEGF family. It plays crucial roles in both lymphangiogenesis (formation of lymphatic vessels) and angiogenesis (formation of blood vessels). VEGF-D is initially synthesized as a precursor protein that undergoes proteolytic processing to generate the mature, biologically active form. The protein functions through binding to VEGF receptor 3 (VEGFR-3/Flt-4) and, in its mature form, can also bind to VEGFR-2 (KDR/Flk-1).

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Biological Functions

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Lymphangiogenesis

  • Lymphatic Development: Essential for lymphatic vessel formation during development
  • Lymphatic Sprouting: Promotes sprouting and branching of lymphatic capillaries
  • Lymphatic Remodeling: Involved in lymphatic vessel maturation and remodeling
  • Fluid Homeostasis: Maintains tissue fluid balance through lymphatic function

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Angiogenesis

  • Blood Vessel Formation: Stimulates endothelial cell proliferation and migration
  • Vascular Sprouting: Promotes new blood vessel formation from existing vessels
  • Wound Healing: Important for vascular repair and tissue regeneration
  • Pathological Angiogenesis: Involved in tumor vascularization

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Disease Associations

  • Cancer Metastasis: Facilitates tumor spread through lymphatic vessels
  • Lymphedema: Dysfunction leads to lymphatic disorders
  • Inflammatory Diseases: Elevated in various inflammatory conditions
  • Cardiovascular Disease: Role in vascular remodeling and repair

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Target Details

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Research Applications

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Cancer Research

  • Metastasis Studies: Understanding lymphatic spread of cancer
  • Tumor Angiogenesis: Role in tumor blood vessel formation
  • Therapeutic Target: Anti-VEGF-D strategies for cancer treatment
  • Biomarker Development: VEGF-D levels as prognostic indicators

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Lymphatic Biology

  • Development: Understanding lymphatic system development
  • Disease Models: Studying lymphatic disorders and dysfunction
  • Regenerative Medicine: Promoting lymphatic vessel regeneration
  • Tissue Engineering: Engineering lymphatic networks in tissue constructs

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Cardiovascular Research

  • Vascular Biology: Understanding blood vessel formation and maintenance
  • Ischemia Models: Therapeutic angiogenesis for tissue repair
  • Vascular Disease: Role in atherosclerosis and vascular remodeling
  • Wound Healing: Promoting vascularization in wound repair

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Therapeutic Potential

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Cancer Therapy

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Anti-VEGF-D Approaches

  • Monoclonal Antibodies: Blocking VEGF-D activity
  • Receptor Antagonists: VEGFR-2/3 inhibitors
  • Soluble Receptors: Trap ligands to prevent signaling
  • Combination Therapy: With other anti-angiogenic agents

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Metastasis Prevention

  • Lymphatic Blockade: Preventing lymphatic metastasis
  • Dual Targeting: Blocking both angiogenesis and lymphangiogenesis
  • Early Intervention: Targeting pre-metastatic niche formation

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Regenerative Medicine

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Pro-Lymphangiogenic Therapy

  • Lymphedema Treatment: Promoting lymphatic vessel regeneration
  • Tissue Transplantation: Improving graft lymphatic integration
  • Wound Healing: Enhancing lymphatic drainage in chronic wounds
  • Inflammatory Diseases: Modulating lymphatic function in inflammation

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Angiogenic Therapy

  • Ischemic Diseases: Promoting blood vessel formation
  • Diabetic Complications: Treating vascular complications
  • Wound Healing: Enhancing vascularization
  • Tissue Engineering: Vascularizing tissue constructs

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Clinical Relevance

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Biomarker Applications

  • Cancer Prognosis: Serum VEGF-D levels correlate with metastatic potential
  • Treatment Response: Monitoring anti-angiogenic therapy efficacy
  • Disease Progression: Tracking cancer advancement
  • Lymphatic Function: Assessing lymphatic system health

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Diagnostic Applications

  • Imaging: VEGF-D-targeted imaging agents
  • Lymphoscintigraphy: Functional lymphatic imaging
  • Biopsy Analysis: Tissue VEGF-D expression patterns
  • Liquid Biopsy: Circulating VEGF-D measurements

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Drug Development Challenges

  • Selectivity: Distinguishing between VEGF family members
  • Delivery: Targeting specific tissue compartments
  • Safety: Avoiding disruption of normal lymphatic function
  • Efficacy: Achieving sufficient pathway inhibition

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Research Tools and Methods

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In Vitro Assays

  • Binding Studies: VEGF-D receptor binding assays
  • Cell Proliferation: Endothelial cell growth assays
  • Migration Assays: Cell motility and invasion studies
  • Tube Formation: Angiogenesis and lymphangiogenesis models

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In Vivo Models

  • Xenograft Studies: Tumor angiogenesis and metastasis
  • Lymphatic Development: Developmental biology studies
  • Disease Models: Lymphedema, cancer, inflammatory diseases
  • Therapeutic Studies: Efficacy testing of VEGF-D modulators

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Analytical Methods

  • ELISA: Quantitative VEGF-D measurement
  • Western Blotting: Protein expression analysis
  • Immunohistochemistry: Tissue localization studies
  • Flow Cytometry: Receptor expression analysis

VEGF-D is available in our target library in both the precursor and mature forms. The mature form (Phe 93 - Ser 201) is most commonly used for binding studies as it represents the biologically active state that binds to both VEGFR-2 and VEGFR-3.

When studying VEGF-D binding, consider that the protein exists in multiple forms (precursor vs. mature) with different receptor binding specificities. The mature form has broader receptor binding capability and higher biological activity than the precursor form.