@misc{oai:repo.qst.go.jp:00070802,
 author = {Nakayama, Fumiaki and Umeda, Sachiko and Yasuda, Takeshi and Asada, Masahiro and Motomura, Kaori and Imamura, Toru and Imai, Takashi and 中山 文明 and 梅田 禎子 and 安田 武嗣 and 今井 高志},
 month = {Jun},
 note = {Radiation-induced hair loss is a clinically important topic because it influences the patients negatively to decide to choose radiation therapy. Several fibroblast
growth factors (FGFs) have been found to be able to protect against radiation damage. In particular, FGF1 is able to activate all of the known tyrosine kinase
FGFR subtypes and is responsible for many biological effects, so that the wide spectrum of FGF1 activity was expected to be advantageous to treat radiation
injuries. However, FGF1 has poor thermal stability and a relatively short half-life in vivo; therefore, the structural instability of FGF1 limits its potential for practical
use. Hence, an FGF1 triple mutant Q40P/S47I/H93G was created as the most stable and active FGF1. Q40P/S47I/H93G had the same receptor specificity as
wild-type FGF1 and the in vitro mitogenic activity of Q40P/S47I/H93G in the absence of heparin was at least 10 times stronger than wild-type FGF1. In addition,
Q40P/S47I/H93G had the potent protective effects against radiation-induced intestinal damage and prolonged mouse survival after total body irradiation (TBI)
because of the repair of intestinal damage. To evaluate its effects against radiation-induced hair follicle damage, a portion of the dorsal skin, harboring uniform
telogen phase hair follicles, was depilated from 7-week-old male BALB/c mice to induce the anagen phase of the hair growth cycle. Then, these mice received
TBI with gamma-rays 6 days after depilation to induce hair follicle dystrophy. Under these conditions, hair could grow after irradiation at 4 Gy, but not at more than
6 Gy, and K15 positive stem cells decreased in anagen hair follicles in a radiation dose-dependent manner. When Q40P/S47I/H93G or wild-type FGF1 in the
absence of heparin was administered intraperitoneally 24 h before irradiation, Q40P/S47I/H93G treatment significantly decreased TUNEL-positive cells in hair
bulbs 24 h after TBI at 12 Gy compared with wild-type FGF1. Treatment with Q40P/S47I/H93G noticeably decreased the appearance of activated caspase 3-
positive cells in hair bulbs in a dose-dependent manner 8 h after irradiation, but not with wild-type FGF1. In addition, Q40P/S47I/H93G enhanced BrdU
incorporation in hair bulbs after irradiation. Q40P/S47I/H93G maintains the number of K15 positive stem cells in the bulge regions of hair follicles 3 days after TBI
at 4 Gy, although wild-type FGF1 could not prevent the decrease of K15 positive stem cells. Moreover, K15 positive cells increased in the lower outer sheath after
Q40P/S47I/H93G treatment. These findings suggest that the structural stability of FGF1 can increase the capability for self-renewal of stem cells, resulting in the
maintenance of stem cells in their differentiation. Therefore, Q40P/S47I/H93G may be a candidate for the treatment or prevention of hair loss after radiation
therapy., ISSCR2012},
 title = {Stabilization of fibroblast growth FACTOR-1 improved radiation-induced hair follicle dystrophy with the maintenance of hair follicle stem cells},
 year = {2012}
}