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Fibroblast growth factor (FGF) is a cell growth factor isolated from the bovine pituitary gland that promotes cell growth and proliferation. Studies demonstrate that FGF is a multifunctional peptide growth factor family that is highly conserved throughout the animal kingdom. The mammalian FGF family comprises 23 peptides that regulate the migration, proliferation, differentiation, survival, and metabolic and neural functions of various cells. Acidic FGF (aFGF) and basic FGF (bFGF) are characteristic members of the FGF family, with their primary distinction lying in their isoelectric points. Furthermore, FGF is categorized into the paracrine subfamily (FGF1, FGF4, FGF7, FGF8, FGF9), endocrine subfamily (FGF19), and intracellular subfamily (FGF11) according to their secretion types.
Figure 1. Mechanism of action of secreted FGFs and identified underlying signaling. (Khosravi F, et al., 2021)
FGF1 plays an important role in adaptive fat remodeling. In adipose tissue, FGF1 can strongly respond to feeding signals and high-fat diet signals and is highly expressed under the regulation of related signals. Recent studies have found that mice lacking FGF1 exhibit a more severe diabetic phenotype under high-fat dietary conditions. However, exogenous FGF1 injection can rapidly reduce blood glucose levels in diabetic mouse models by acting on adipocyte FGF receptors (FGFR1). Thus, FGF1 could serve as a novel regulator of fatty acid homeostasis and a potential target for the treatment of type 2 diabetes.
FGF2 is a pleiotropic cytokine that not only promotes cell proliferation and angiogenesis but also participates in a variety of biological processes such as the repair of tissue damage and induction of embryonic development. It has been found that FGF2 is related to the pathogenesis of emphysema and plays an important role in lung repair after injury. Endogenous FGF2 can promote the proliferation and differentiation of alveolar epithelial cells and thus promote lung tissue repair, thus providing a new therapeutic means for the treatment of lung injury.
FGF7 is essential for organogenesis and tissue patterning in the embryo as well as mediating wound healing and tissue homeostasis in adult mammals and is required for kidney, thymus, and hippocampus development. In addition, FGF7 is involved in mammary gland development and breast cancer development. In breast cancer, aberrant expression of FGF7 is associated with tumor invasion and metastasis.
FGF8 is an essential cellular regulator during embryonic development and can regulate the formation of gastrula embryo. It has been demonstrated that FCF8 gene inactivation leads to embryonic death in mice. However, overexpression of FGF8 can be detected in human prostate and ovarian cancer cells, resulting in persistent androgen-independent disease. In clinical prostate cancer, the expression of FGF8 is more pronounced than that of other FGF family members.
FGF10 is a typical paracrine growth factor, which is neuroprotective in spinal cord injury and cerebral ischemic injury models in rats. Numerous data confirm that FGF10 promotes motor and sensory function recovery in sciatic nerve injury and facilitates peripheral nerve regeneration through PI3K/Akt signaling.
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