@article{oai:repo.qst.go.jp:00047755,
 author = {Kawano, Mitsuko and Umeda, Sachiko and Yasuda, Takeshi and Fujita, Mayumi and Ishikawa, Atsuko and Imamura, Toru and Imai, Takashi and Nakayama, Fumiaki and 川野 光子 and 梅田 禎子 and 安田 武嗣 and 藤田 真由美 and 石川 敦子 and 今村 亨 and 今井 高志 and 中山 文明},
 issue = {3},
 journal = {Advances in Radiation Oncology},
 month = {Jun},
 note = {Purpose
Telogen (resting phase) hair follicles (HFs) are more radioresistant than their anagen (growth phase) counterparts. Fibroblast growth factor (FGF) 18 is strongly expressed in telogen HFs to maintain the telogen phase, while several other FGFs exert radioprotective effects. However, the role of FGF18 in the radioresistance of HFs remains unknown. Therefore, this study focused on clarifying the role of FGF18 in the radioresistance of telogen HFs and its potential as a radioprotector.
\nMethods and Materials
BALB/c mice with telogen or plucking-induced anagen HFs were exposed to total body irradiation with γ-rays at 4 to 12 Gy after intraperitoneal treatment with a FGF18 or FGFR inhibitor. A time course analysis was performed histologically and hair growth was observed 14 or 15 days after depilation. Skin specimens were analyzed by DNA microarrays and western blotting.
\nResults
Telogen irradiation at 6 Gy resulted in transient cell growth arrest, leading to successful hair growth, whereas anagen irradiation failed to promote hair growth. Telogen irradiation did not induce apoptosis in HFs or reduce hair follicle stem cells, whereas anagen irradiation induced apoptosis and reduced stem cell numbers. The Inhibition of FGF receptor signaling during the telogen phase promoted HF cell proliferation; however, hair failed to grow after irradiation. In contrast, recombinant FGF18 induced transient cell growth arrest after anagen irradiation with enhanced DNA repair, leading to the inhibition of apoptosis, maintenance of hair follicle stem cells, and successful hair growth. Moreover, FGF18 reduced the expression levels of genes promoting G2/M transition as well as the protein expression levels of cyclin B1 and cdc2 in skin, and induced G2/M arrest in the keratinocyte cell line HaCaT.
\nConclusion
These results suggest that FGF18 signaling mediates radioresistance in telogen HFs by arresting the cell cycle, and that FGF18 has potential as a radioprotector for radiation-induced alopecia.},
 pages = {170--181},
 title = {FGF18 Signaling in the Hair Cycle Resting Phase Determines Radioresistance of Hair Follicles by Arresting Hair Cycling},
 volume = {1},
 year = {2016}
}