Abstract
Fibroblast growth factors (FGFs) are a large family of secretory molecules that act through tyrosine kinase receptors known as FGF receptors. They play crucial roles in a wide variety of cellular functions, including cell proliferation, survival, metabolism, morphogenesis, and differentiation, as well as in tissue repair and regeneration. The signaling pathways regulated by FGFs include RAS/mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)–protein kinase B (AKT), phospholipase C gamma (PLCγ), and signal transducer and activator of transcription (STAT). To date, 22 FGFs have been discovered, involved in different functions in the body. Several FGFs directly or indirectly interfere with repair during tissue regeneration, in addition to their critical functions in the maintenance of pluripotency and dedifferentiation of stem cells. In this review, we summarize the roles of FGFs in diverse cellular processes and shed light on the importance of FGF signaling in mechanisms of tissue repair and regeneration.
Highlights
Fibroblast growth factors (FGFs) are a family of cell-signaling proteins produced by different types of cells
We summarize the roles of FGFs in diverse cellular processes and shed light on the importance of FGF signaling in mechanisms of tissue repair and regeneration
In invertebrates and lower vertebrates, FGF is crucial for regeneration, whereas in higher vertebrates, it mediates the mechanisms of wound healing and tissue repair
Summary
FGFs are a family of cell-signaling proteins produced by different types of cells. The first members of the fibroblast growth factor (FGF) family (FGF1 and FGF2) were discovered in the 1970s and were initially named acidic and basic FGF, respectively [1]. FGFs can affect the proliferation of multiple cells, including endothelial cells, neurons, chondrocytes, smooth-muscle cells, melanocytes, and adipocytes [2] They are involved in a variety of biological processes, including cellular proliferation, survival, metabolism, morphogenesis, differentiation, embryonic development, angiogenesis, tissue repair, and regeneration [3]. Cancer-associated fibroblasts are activated fibroblasts that serve as a key component of the tumor microenvironment [16] They trigger the MEK–extracellular signal-regulated kinase (ERK) pathway and modulate MMP7 through FGFR4 to stimulate cancer cell growth and angiogenesis [17]. The presence of mature blood vessels is very helpful for boosting tissue repair Both acidic and basic FGF (bFGF) are involved in angiogenesis in particular ways. These new insights into the functions of FGFs in tissue repair and regeneration are summarized in this review
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