Fibroblast Growth Factors (FGFs) are a large family of growth factors involved in various biological processes, including cell growth, differentiation, angiogenesis, wound healing, and embryonic development. FGFs play crucial roles in both normal physiology and pathological conditions, exerting their effects through interaction with specific cell surface receptors known as FGF receptors (FGFRs).

• Structure:
  • Family Members: The FGF family comprises 22 members in humans, designated FGF1 through FGF23 (with the exception of FGF15, which is specific to rodents). These proteins range in size from 17 to 34 kDa.
  • Core Domains: FGFs share a conserved core domain that facilitates binding to FGFRs. However, they also have unique sequences that confer specific binding properties and biological functions.
  • Heparin Binding: Many FGFs require heparin or heparan sulfate proteoglycans (HSPGs) for stable binding to FGFRs, enhancing receptor affinity and specificity.
• Receptor Binding and Signaling:
  • FGF Receptors (FGFRs): FGFs exert their effects by binding to FGFRs, which are transmembrane receptor tyrosine kinases. There are four FGFRs (FGFR1-FGFR4), each with multiple isoforms due to alternative splicing.
  • Dimerization and Activation: FGF binding induces dimerization of FGFRs, leading to autophosphorylation of specific tyrosine residues in the intracellular domain. This activation triggers downstream signaling cascades.
  • Key Pathways Activated:
    • MAPK/ERK Pathway: Regulates cell proliferation, differentiation, and survival.
    • PI3K/AKT Pathway: Promotes cell survival and metabolism.
    • PLCγ Pathway: Involved in intracellular calcium signaling and modulation of cell shape and motility.
• Biological Functions:
  • Cell Proliferation and Differentiation: FGFs are vital for the proliferation and differentiation of a wide range of cell types, including fibroblasts, endothelial cells, and neural cells.
  • Angiogenesis: FGFs, particularly FGF2 (basic FGF), are potent angiogenic factors that promote the formation of new blood vessels, crucial in wound healing and tissue repair.
  • Wound Healing: FGFs accelerate wound healing by stimulating the proliferation and migration of fibroblasts and endothelial cells, leading to tissue regeneration and repair.
  • Development: FGFs are key regulators of embryonic development, influencing processes such as limb formation, neural development, and organogenesis.
• Applications in Research and Medicine:
  • Cell Culture: FGFs are commonly used in cell culture media to support the growth and maintenance of specific cell types, including stem cells, endothelial cells, and fibroblasts.
  • Tissue Engineering: FGFs are used to promote cell growth and tissue regeneration in engineered tissues, particularly in skin, bone, and blood vessels.
  • Wound Healing Therapies: FGFs are incorporated into therapeutic products to enhance wound healing, particularly in chronic wounds, burns, and ulcers.
  • Cancer Research: FGFs and FGFRs are implicated in cancer biology, as dysregulated FGF signaling can lead to tumor growth, angiogenesis, and metastasis. FGFR inhibitors are being developed as potential cancer therapies.
  • Metabolic Disorders: FGFs like FGF21 are being explored as potential treatments for metabolic disorders such as obesity and diabetes due to their roles in regulating glucose and lipid metabolism.
• Clinical Implications:
  • Cancer: Abnormal FGF signaling is associated with various cancers, including breast, lung, and bladder cancers. Targeting FGFR signaling is a therapeutic strategy being pursued in oncology.
  • Developmental Disorders: Mutations in FGFRs can lead to congenital disorders such as craniosynostosis and skeletal dysplasia. Understanding FGF signaling is key to developing treatments for these conditions.
  • Cardiovascular Disease: FGF1 and FGF2 are involved in cardiac repair and regeneration, and are being investigated for their potential in treating heart disease.