For this Growth Factor Focus week, we want to take a closer look at the FGF7 subfamily of Fibroblast Growth Factors (FGFs). At Gold Bio, we have human, mouse and rat FGF10 as well as both human and mouse FGF7 available for research purposes. FGFs form one of the largest families of growth factors. They are found in nearly all multicellular lifeforms, ranging from nematodes to humans. They are crucial in the embryonic development process; responsible for developing the vascular system, CNS system, the mesoderm, limb development, branching morphogenesis and even brain patterning.
The three major members of the FGF7 Subfamily are FGF7, FGF10 and FGF22. Historically, FGF3 has also been grouped into this subfamily based on phylogenetic or functional analysis, but its best association is still being debated in literature. Itoh and Ornitz (2008) further described that FGF3 is actually closer to FGF4 and FGF6 based on gene location and should probably be associated with that family instead. (Click on the thumbnail for a gene location map of the 7 subfamilies characterized by Itoh and Ornitz.)
The main characterization of the FGF7 subfamily is its specificity with the FGF2Rb receptor. Kuro-o (2012) describes the β1 strands of these growth factors as being “extended two residues N-terminally due to additional strand pairing with β4.” This critical extension allows the FGF7 subfamily to engage specifically with the βC’- βE loop of the FGFR2b. Interestingly, that extension also clashes with the loop of FGFR2c, actively discouraging any binding of the FGF7 subfamily to that receptor.
FGF7 and FGF10 are also known as KGF1 and KGR2, or Keratinoncyte Growth Factors. Keratinocytes are the predominant cells in the epidermal (outermost) layer of the skin. As the epidermis is damaged, additional keratinocytes are induced by growth factors and cover over the wound bed, creating a new barrier over the healing tissue. FGF7 levels increase 150 fold in skin after cutaneous injury (Beenken, 2009). But these growth factors are also crucial in embryonic development of the mesenchymal tissue. Disruption of FGF10 signaling has been shown to result in severe defects in limb development and branching organs, like the pancreas, lungs or salivary glands (Zhang, 2006).
A truncated version of FGF7, known as Palifermin (or Kepivance under Biovitrum), is currently an FDA approved treatment for use during cancer therapies. Palifermin is used for the treatment of oral mucositis, a common side effect of high dosage radiation or chemotherapy for bone marrow transplants or leukemia. According to Beenken, et al. (2009), “when administered on 3 consecutive days before high-dose chemotherapy, as well as for 3 days following haematopoietic stem cell transplantation, Palifermin reduced the median duration of mucositis from 9 to 6 days, and reduced the incidence of grade 4 mucositis from 62% to 20%. This corresponds with a significant improvement in the patients’ quality of life, as grade 4 mucositis is of such severity that oral feeding is impossible.”
Stay tuned for next week’s Growth Factor Highlight and if you have questions or would just like to learn more about these products, please email us at [email protected]!
Itoh, Nobuyuki, and David M. Ornitz. “Functional evolutionary history of the mouse Fgf gene family.” Developmental Dynamics 237.1 (2008): 18-27.
Kuro-o, Makoto, ed. Endocrine FGFs and klothos. Vol. 728. Springer, 2012.
Zhang, Xiuqin, et al. “Receptor specificity of the fibroblast growth factor family.” Journal of Biological Chemistry 281.23 (2006): 15694-15700.
Umemori, Hisashi, et al. “FGF22 and its close relatives are presynaptic organizing molecules in the mammalian brain.” Cell 118.2 (2004): 257-270.
Oulion, Silvan, Stephanie Bertrand, and Hector Escriva. “Evolution of the FGF Gene Family.” International Journal of Evolutionary Biology 2012 (2012).
Beenken, Andrew, and Moosa Mohammadi. “The FGF family: biology, pathophysiology and therapy.” Nature Reviews Drug Discovery 8.3 (2009): 235-253.
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