VEGFVEGFR

VEGF-VEGFR refers to the signaling axis formed by vascular endothelial growth factors (VEGF) and their receptors (VEGFRs). The VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). These ligands bind to receptor tyrosine kinases VEGFR-1 (FLT1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (FLT4). VEGFR-2 is the principal mediator of angiogenic responses in blood vessels, while VEGFR-3 mainly drives lymphangiogenesis. VEGF signalling is modulated by co-receptors such as neuropilins (NRP1, NRP2) that enhance ligand binding and receptor activation.

VEGF expression is upregulated by hypoxia and other stimuli via transcription factors such as HIF-1. Ligand binding induces VEGFR dimerization and autophosphorylation, activating downstream pathways including PI3K-AKT, Ras-ERK, PLCγ, and Src. Consequences include endothelial proliferation, migration, survival, increased permeability, and tubular morphogenesis. The VEGF-VEGFR axis is essential for embryonic vasculogenesis and placental vascular development and remains important for wound healing, follicular development, and tissue regeneration in adults.

Dysregulation of VEGF-VEGFR signalling is implicated in disease, particularly cancer and ocular neovascular disorders such as age-related macular degeneration and diabetic retinopathy. Therapeutic strategies aim to block VEGF signalling, including anti-VEGF antibodies (e.g., bevacizumab), soluble VEGF traps, and receptor tyrosine kinase inhibitors (e.g., sunitinib, sorafenib, axitinib, pazopanib). Limitations include resistance and adverse effects such as hypertension and thrombosis. Ongoing research seeks to improve targeting, overcome resistance, and exploit VEGF-VEGFR biology for regenerative medicine.