Analysis of hair growth by growth factors and their related molecules.
| Project/Area Number |
15591196
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
TSUBOI Ryoji Tokyo Medical University, Medicine, Professor, 医学部, 教授 (70221421)
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| Co-Investigator(Kenkyū-buntansha) |
SETOGUCHI Yasuhiro Tokyo Medical University, Medicine, Associate Professor, 医学部, 助教授 (90206649)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | hair growth / FGF-5 / FGFR-1 / Smad / TGF-β / antisense / FCF-5 / antisense / FGFR1 / Smads |
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| Research Abstract |
The Smad family of proteins mediates signal transduction of the TGF-β superfamily. Smad 3 stimulates TGF-β signal and Smad 7 suppresses it. To determine the role of Smad proteins, an in vitro type I collagen gel contraction assay was performed using human dermal fibroblasts. The recombinant E-1 deleted adenoviral vectors carrying mouse Samd3, Smad7 or lacZ cDNA under the cytomegalovirus promoters were infected into humans dermal fibroblasts. Overexpression of Smad3 enhanced collagen gel contraction by fibroblasts when compared with fibroblasts overexpressing a control lacZ. In contrast, TGF-β-mediated collagen gel contraction was suppressed by overexpression of Smad7 in fibroblasts. Moreover, IFN-γ failed to antagonize the contractile activity of keloid-derived fibroblast embedded collagen gel.
The hair cycle is regulated by various molecules, among which FGF-5 has been shown to promote the transition from anagen to catagen. FGFR-1, a trans-membrane receptor of FGF-5, is localized in th
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e follicular papilla of hair follicles. In order to apply the antisense oligonucleotides targeting FGFR-1 as a treatment for baldness, we examined the effect of the oligonucleotides on hair follicle growth in a serum-free organ culture system. Vibrissal hair follicles from C3H/He mice were cultured in the presence of a reagent at 31℃ in 95% O2-5% CO2 for 72 h. A 20-mer antisense nucleotide and its randomly arranged counterpart were prepared by predicting the effective target site of FGFR-1 mRNA. Cellular activity in the hair bulb was estimated by measuring the fluorescence intensity (FI) of the medium after incubation with AlamarBlue dye. The addition of 30 μM of the phosphorothioate form of antisense oligonucleotide to the media, increased FI by 30% whereas the control produced no detectable change. However, neither oligonucleotides demonstrated further elongation of the hair shaft as compared with the control group. These results suggest the clinical utility of antisense nucleotide targeting FGFR- 1 as a treatment for baldness.
Ketoconazole (KCZ) is an imidazole anti-fungal agent that is also effective in topical applications for treating seborrheic dermatitis and dandruff. Topical applications of 2% KCZ to the back skin of C3H/He mice had a macroscopically significant stimulatory effect on hair growth compared with the vehicle group (p<0.01, n=10), suggesting that ketoconazol is useful as a hair growth stimulant. Less
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Report
(3 results)
Research Products
(13 results)
