Comprehensive Analysis of FGF and FGFR Expression in Skin: FGF18 Is Highly Expressed in Hair Follicles and Capable of Inducing Anagen from Telogen Stage Hair Follicles

Abstract

We quantified the mRNA expression of all 22 fibroblast growth factor family members (FGF) and their four receptors (FGFR) in adult mouse full-thickness skin at various stages of the hair growth cycle. We found that in addition to mRNA encoding FGF previously identified in skin (FGF1, 2, 5, 7, 10, 13, and 22), FGF18 mRNA was also strongly expressed. Expression of these FGF varied throughout hair growth cycle: mRNA expression of FGF18 and 13 peaked at telogen; FGF7 and 10 at anagen V; and FGF5 and 22 at anagen VI. In situ hybridization revealed that FGF18 mRNA is mainly expressed in the anagen inner root sheath and telogen bulge of hair follicles. In culture, FGF18 stimulated DNA synthesis in human dermal fibroblasts, dermal papilla cells, epidermal keratinocytes and vascular endothelial cells. When FGF18 was administered subcutaneously to mice in a uniform telogen state, anagen hair growth was observed. Our findings suggest that FGF18 is important for the regulation of hair growth and the maintenance of skin in adult mice.

Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice

“…Earlier studies have shown that FGF1, 2, 5, 7, 10, 13 and 22 are all highly expressed in the skin of C3H/HeN mice and that many of them play important roles in skin and/or hair dynamics (DuCros et al 1993, Hebert et al 1994, Danilenko et al 1995, Guo et al 1996, Rosenquist & Martin 1996, Mitsui et al 1997, Ortega et al 1998, Suzuki et al 1998, Nakatake et al 2001, Beyer et al 2003, Steiling & Werner 2003, Kawano et al 2004, 2005. Moreover, we have found that expression of these factors is strongly affected by the progress of the hair growth cycle (Kawano et al 2004(Kawano et al , 2005.…”

“…Moreover, we have found that expression of these factors is strongly affected by the progress of the hair growth cycle (Kawano et al 2004(Kawano et al , 2005. For that reason, we examined wound healing in the hairless mouse to eliminate the effect of the hair growth cycle on FGF expression.…”

“…Moreover, FGF7 (or keratinocyte growth factor, KGF), FGF10 (or KGF2), and possibly FGF22 act in concert via FGF receptor 2 IIIb (FGFR2 IIIb) to stimulate keratinocyte proliferation in both normal and wounded skin (Werner et al 1994, Marchese et al 1995, Igarashi et al 1998, Ohuchi et al 2000, Beyer et al 2003, and overexpression of a dominant negative form of FGFR2 IIIb severely delays wound re-epithelialization in the transgenic mice (Werner et al 1994). In addition, FGF1 (or acidic FGF), 2 (or basic FGF), 13 (or FGF-homologous factor-2; FHF2) and 18 are reportedly expressed in dermal and hair follicular cells (Marchese et al 1995, Ortega et al 1998, Kawano et al 2004, 2005 and regulate skin regeneration and hair growth, although the activity of FGF13 is not yet clear. Finally, the overlapping but differential binding specificity of FGF family members to their respective receptors suggests that as yet uncharacterized FGFs may also contribute to wound healing.…”

Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

“…FGF-7 is known to induce and maintain anagen hair follicle growth. FGF-7 expression in the hair follicle dermal papilla was up-regulated during the anagen phase (20). Furthermore, addition of FGF-7 to a hair organ culture medium causes a decrease in the number of follicles in the catagen phase compared to the number of follicles in an (A) DP cells were cultured with adenosine at the indicated concentrations for 18 h. Total-RNA was isolated from both control DP cells and cells treated with adenosine at the indicated concentrations after 18 h, reverse-transcribed, and a polymerase chain reaction was performed for fibroblast growth factor receptors 7 and 2 (FGF-7, FGF-2), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and glyceraldehyde-3-phosphate dehydrogenase (G3PDH).…”

Fundamental hair follicle biology and fine fibre production in animals

“…The binding protein Igfbp 3 has been shown to be increased in expression in DP cells during regression and early telogen, with Igfbp 5 evident during anagen. Similarly, Kawano et al (2005), analysed murine skin samples for expression of the 22 genes encoding for members of the FGF family of secreted growth factors and for the four FGF RTK genes. Attention was drawn to previous reports of the effect of FGF 5, expressed in the ORS, in the induction of catagen (Hé bert et al, 1994) and the antagonistic effect of FGF 5S.…”