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Structural Stability of Human Fibroblast Growth FACTOR-1 is Essential for Protective Effects Against Radiation-Induced Intestinal Damage.
https://repo.qst.go.jp/records/48381
https://repo.qst.go.jp/records/483817a75aa46-1e44-4a71-a966-2546242cc718
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-11-22 | |||||
| タイトル | ||||||
| タイトル | Structural Stability of Human Fibroblast Growth FACTOR-1 is Essential for Protective Effects Against Radiation-Induced Intestinal Damage. | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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× Suzuki, Masashi× Zakrzewska, Malgorzata× Imamura, Toru× Imai, Takashi× 中山 文明× 梅田 禎子× 安田 武嗣× 今村 亨× 今井 高志 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Purpose: FGF1 has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with gamma-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Pre-irradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and post-irradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by post-irradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, pre-irradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal damage. Therefore, Q40P/S47I/H93G is pharmacologically one of the most promising candidates for clinical applications for radiation-induced gastrointestinal syndrome. |
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| 書誌情報 |
International Journal of Radiation Oncology Biology Physics 巻 85, 号 2, p. 477-483, 発行日 2012-06 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0360-3016 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.ijrobp.2012.04.042 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.sciencedirect.com/science/article/pii/S0360301612006396 | |||||
| 関連名称 | http://www.sciencedirect.com/science/article/pii/S0360301612006396 | |||||
