Fibroblast Growth Factor (FGFs)

Fibroblast Growth Factors (FGFs): Overview and Functions

Definition

Fibroblast growth factors (FGFs) are a large family of polypeptides that play essential roles in various biological processes, including embryonic development, tissue repair, and regulation of cell growth and differentiation. FGFs exert their effects by binding to specific fibroblast growth factor receptors (FGFRs), which are receptor tyrosine kinases that initiate intracellular signaling cascades.

Types of FGFs

There are 22 known FGFs in humans, classified into different subfamilies based on their structural and functional characteristics. Key members include:

• FGF1 and FGF2: The first FGFs discovered; they are involved in wound healing and angiogenesis.
• FGF3, FGF4, and FGF8: Important for embryonic development and organogenesis.
• FGF7 (also known as keratinocyte growth factor): Plays a crucial role in epithelial cell proliferation and survival.

Mechanism of Action

• Receptor Binding:

• FGFs bind to FGFRs on the cell surface, leading to receptor dimerization. This dimerization activates the intrinsic tyrosine kinase activity of the receptors.

• Autophosphorylation:

• Upon activation, FGFRs undergo autophosphorylation on specific tyrosine residues, creating docking sites for downstream signaling molecules.

• Signaling Pathways:

• FGF signaling activates several key pathways, including:
  • MAPK Pathway: Involved in regulating chttps://drstemcellsthailand.com/cell-proliferation/ and differentiation.
  • PI3K/Akt Pathway: Promotes cell survival and metabolism.
  • PLCγ Pathway: Involved in calcium signaling and cellular responses.

Biological Functions

• Embryonic Development:

• FGFs are critical for various developmental processes, including germ layer formation, limb development, and organogenesis. They regulate cell fate decisions and tissue patterning during embryogenesis.

• Tissue Repair and Regeneration:

• FGFs play a vital role in wound healing by promoting angiogenesis (formation of new blood vessels) and stimulating the proliferation of fibroblasts and epithelial cells at injury sites.

• Neurogenesis:

• Certain FGFs are involved in neural development, influencing neuronal proliferation, differentiation, and axon growth. For instance, FGF2 is known to enhance neurite outgrowth in neurons .

• Metabolism Regulation:

• FGFs also function as metabolic regulators. For example, FGF21 is involved in glucose homeostasis and lipid metabolism.

Clinical Implications

• Cancer:

• Dysregulation of FGF signaling is implicated in various cancers, where abnormal FGF/FGFR interactions can promote tumor growth, metastasis, and resistance to therapies.

• Fibrotic Diseases:

• Overactivation of FGF signaling can contribute to fibrotic conditions by promoting excessive collagen deposition and scar formation in tissues such as the lungs (pulmonary fibrosis) and liver (cirrhosis).

• Therapeutic Targets:

• Given their roles in disease processes, FGFs and their receptors are being explored as therapeutic targets for developing new treatments for cancer, metabolic disorders, and regenerative medicine.

Conclusion

Fibroblast growth factors are essential signaling molecules that regulate a wide range of biological processes from embryonic development to tissue repair. Their involvement in various diseases highlights their potential as targets for therapeutic interventions.

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References

1. Nature Reviews Molecular Cell Biology. (2020). “FGF/FGFR signaling in health and disease.” Retrieved from Nature.
2. BioMed Central. (2023). “Fibroblast growth factor signaling in axons: from development to disease.” Retrieved from BioSignaling.
3. PMC Articles. (2021). “Functional Roles of FGF Signaling in Early Development of Vertebrates.” Retrieved from NCBI.
4. Frontiers in Cell and Developmental Biology. (2020). “The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair.” Retrieved from Frontiers.
5. Journal of Biological Chemistry. (2022). “Fibroblast Growth Factors: From Molecular Evolution to Roles in Disease.” Retrieved from Oxford Academic.