Fibroblast Growth Factor (FGF)
A family of growth factors that stimulate fibroblast proliferation, angiogenesis, and tissue development. FGFs play key roles in wound healing, embryonic development, and tissue homeostasis. FGFR3 mutations cause achondroplasia — the condition treated by the CNP analogue vosoritide.
Technical Context
The FGF family comprises 22 members (FGF1-23, with FGF15 being the mouse orthologue of human FGF19) acting through 4 receptor tyrosine kinases (FGFR1-4). In wound healing, FGF-2 (basic FGF) is the most relevant — it stimulates fibroblast proliferation, angiogenesis (working synergistically with VEGF), and keratinocyte migration. FGFR3 is particularly relevant to peptide therapeutics: gain-of-function FGFR3 mutations cause achondroplasia (the most common form of dwarfism) by constitutively activating the MAPK/ERK pathway in growth plate chondrocytes, inhibiting proliferation and hypertrophy. Vosoritide (a CNP analogue) counteracts this by activating NPR-B → cGMP → PKG-II, which inhibits the RAF-MEK-ERK pathway downstream of FGFR3, restoring growth plate function and enabling bone elongation.