Human VEGF-D
Vascular Endothelial Growth Factor D (VEGF-D) is a key regulator of lymphangiogenesis and angiogenesis with therapeutic potential in cancer and lymphatic disorders.
Human VEGF-D
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).Biological Functions
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
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
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
Target Details
Protein Information
Protein Information
Organism: Homo sapiens (Human)
Gene Name: VEGFD
Alternative Names: c-fos-induced growth factor (FIGF)
Protein Family: PDGF/VEGF family, cystine knot growth factors
Database References
Database References
UniProt ID: O43915
Gene ID: 2277
NCBI Reference: AAH27948
Protein Region: Phe 93 - Ser 201 (mature form)
Structural Information
Structural Information
Molecular Weight: ~21 kDa (mature form), ~43 kDa (precursor)
Structure: Cystine knot motif, homodimer
Key Features: Signal peptide, N- and C-terminal domains, central VEGF homology domain
Processing: Proteolytic cleavage releases mature form
Receptors and Signaling
Receptors and Signaling
Primary Receptor: VEGFR-3 (Flt-4) - lymphangiogenesis
Secondary Receptor: VEGFR-2 (KDR/Flk-1) - angiogenesis (mature form only)
Co-receptors: Neuropilins (Nrp-1, Nrp-2)
Signaling Pathways: PI3K/Akt, MAPK, PLC-γ pathways
Research Applications
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
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
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
Therapeutic Potential
Cancer Therapy
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
Metastasis Prevention
- Lymphatic Blockade: Preventing lymphatic metastasis
- Dual Targeting: Blocking both angiogenesis and lymphangiogenesis
- Early Intervention: Targeting pre-metastatic niche formation
Regenerative Medicine
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
Angiogenic Therapy
- Ischemic Diseases: Promoting blood vessel formation
- Diabetic Complications: Treating vascular complications
- Wound Healing: Enhancing vascularization
- Tissue Engineering: Vascularizing tissue constructs
Clinical Relevance
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
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
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
Research Tools and Methods
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
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
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.