Dual-Mode Regulation of Hair Growth Cycle by Two Fgf-5 Gene Products Satoshi Suzuki, Yutaka Ota  Journal of Investigative Dermatology  Volume 114, Issue 3, Pages 456-463 (March 2000) DOI: 10.1046/j.1523-1747.2000.00912.x Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 FGF-5 inhibited skin pigmentation in mice during anagen. Mice were subcutaneously injected in the dorsal region with PBS (a), FGF-5 (b), or FGF-5S (c) once daily for 7 d beginning 1 d after the induction of anagen (anagen I–anagen V or early anagen VI). The mice were killed on day 8, and skin pigmentation, considered to be an index of hair growth, was observed. Arrows indicate the injection sites. Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 FGF-5 inhibited hair growth in mice during anagen. Mice were subcutaneously injected in the dorsal region with PBS (a), FGF-5 (b), or FGF-5S (c) once daily for 7 d beginning 1 d after the induction of anagen (anagen I–anagen V or early anagen VI), and killed on day 8, as described in Figure 1. Shown are histologic sections representative of the data summarized in Figure 1. Scale bar: 100 μm. D, dermis; PA, panniculus adiposus; hf, hair follicle; dp, dermal papilla. Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 FGF-5 inhibited the growth of hair follicles but did not affect skin thickness in mice during anagen. The experiment began 1 d after the induction of anagen, with mice being injected daily for 7 d, as described in Figure 2. After preparation of the skin sections from the injection sites shown in Figure 2, hair follicle length (a) and the thicknesses of the dermis (b) and panniculus adiposus (c) were measured. Data are expressed as the mean ± SD of five mice; **p <0.01 versus control (Dannett’s multiple comparison). Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Representative histologic sections from mice injected with PBS, FGF-5, or FGF-5S during anagen VI. Mice were subcutaneously injected with PBS (a), FGF-5 (b), or FGF-5S (c) once daily for 8 d beginning on the ninth day after the induction of anagen (during anagen VI). The mice were killed 1 d after the last injection, and skin sections from the injection sites were observed. Scale bar: 100 μm. D, dermis; PA, panniculus adiposus; hf, hair follicle; dp, dermal papilla. Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 FGF-5 promoted involution of anagen hair follicles but did not affect skin thickness. The experiment began on the ninth day after the induction of anagen, with mice being injected daily for 8 d, as described in Figure 4. After preparation of the skin sections from the injection sites shown in Figure 4, hair follicle length (a), the thicknesses of the dermis (b), and panniculus adiposus (c) were measured. Data are expressed as the mean ± SD of five mice; **p <0.01 versus control (Dannett’s multiple comparison). Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Representative histologic sections from mice injected with PBS, FGF-5, or both FGF-5 and FGF-5S during anagen VI. Mice were subcutaneously injected with PBS (a) or FGF-5 (b), or with both FGF-5 and FGF-5S (c), once daily for 8 d starting on the ninth day after the induction of anagen (during anagen VI). The mice were killed 1 d after the last injection, and skin sections from the injection sites were observed. Scale bar: 100 μm. D, dermis; PA, panniculus adiposus; hf, hair follicle; dp, dermal papilla. Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 7 FGF-5S antagonized the effect of FGF-5. Two groups of mice were subcutaneously injected daily for 8 d with either PBS or FGF-5, beginning on the ninth day after the induction of anagen (during anagen VI), whereas a third group was injected with both FGF-5 and FGF-5S, as shown in Figure 6. After preparation of the skin sections of the injection site shown in Figure 6, hair follicle length (a) and the thicknesses of the dermis (b) and panniculus adiposus (c) were measured. Data are expressed as the mean ± SD of five mice. *p <0.05, **p <0.01 (t test). Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 8 Schematic summary of the supposed function of FGF-5-producing macrophage-like cells and FGF-5S in the hair growth cycle. (a) During early anagen, the number of FGF-5-producing macrophage-like cells is small, and little FGF-5S is produced in the hair follicles. (b) During late anagen, the number of FGF-5-producing cells increases in the dermis and FGF-5S, which is now produced in quantity, antagonizes FGF-5. (c) During catagen, FGF-5-producing cells migrate to the panniculus adiposus, gather around dermal papillae and release FGF-5; production of FGF-5S rapidly declines, allowing FGF-5 to bind to its receptor expressed in the dermal papillae. Thereafter, the hair follicles degenerate. D, dermis; PA, panniculus adiposus; hf, hair follicle; dp, dermal papilla; fmc, FGF-5-producing macrophage-like cell. Journal of Investigative Dermatology 2000 114, 456-463DOI: (10.1046/j.1523-1747.2000.00912.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions