FGF

Fibroblast growth factors (FGFs) are a family of signaling proteins that regulate cell proliferation, differentiation, migration, and survival during development and in adult tissues. In mammals, the family comprises 22 members, acting as autocrine or paracrine factors, with several members serving as circulating endocrine hormones, notably FGF19, FGF21, and FGF23.

FGFs exert their effects by binding to FGF receptors (FGFR1–4), receptor tyrosine kinases expressed across tissues. Most FGF–FGFR interactions require heparan sulfate proteoglycans to stabilize the ligand–receptor complex. Endocrine FGFs, having lower affinity for FGFRs, rely on Klotho family co-receptors (alpha- or beta-Klotho) to enable signaling. Ligand binding induces receptor dimerization and activation of downstream pathways such as RAS–MAPK, PI3K–AKT, and PLCγ.

Functions of FGFs span embryonic development, including limb patterning and organogenesis, to adult tissue maintenance. They play a central role in angiogenesis, with FGF2 (basic FGF) being a potent pro-angiogenic factor. FGFs are also involved in wound healing and neurogenesis, and endocrine FGFs regulate metabolism in liver, adipose tissue, and other organs. FGF23 specifically acts on the kidney to regulate phosphate and vitamin D metabolism; FGF19 and FGF21 influence metabolic processes systemically.

Clinical relevance includes the dysregulation of FGFs/FGFRs in cancer, fibrosis, and developmental disorders. FGFR gene amplifications, mutations, or fusions are targets for cancer therapies, and several FGFR inhibitors are approved or in trials. Research into FGF-based therapies continues for wound healing and metabolic diseases. Alternative splicing of FGFRs yields tissue-specific isoforms (IIIb and IIIc) that influence ligand binding, and among FGFs, FGF2 is the basic FGF, while FGF1 is the acidic form.