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Stabilization of fibroblast growth FACTOR-1 improved radiation-induced hair follicle dystrophy with the maintenance of hair follicle stem cells
https://repo.qst.go.jp/records/70802
https://repo.qst.go.jp/records/7080231a492b0-6b60-4256-b051-85ca28d217e6
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-06-19 | |||||
| タイトル | ||||||
| タイトル | Stabilization of fibroblast growth FACTOR-1 improved radiation-induced hair follicle dystrophy with the maintenance of hair follicle stem cells | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Nakayama, Fumiaki
× Nakayama, Fumiaki× Umeda, Sachiko× Yasuda, Takeshi× Asada, Masahiro× Motomura, Kaori× Imamura, Toru× Imai, Takashi× 中山 文明× 梅田 禎子× 安田 武嗣× 今井 高志 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ISSCR2012 | |||||
| 発表年月日 | ||||||
| 日付 | 2012-06-15 | |||||
| 日付タイプ | Issued | |||||
