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Analysis of hair growth by growth factors and their related molecules.

生长因子及其相关分子分析毛发生长。

基本信息

批准号：
15591196
负责人：
TSUBOI Ryoji
金额：
$ 2.11万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591196/
关键词：
hair growth FGF-5 FGFR-1 Smad TGF-β antisense FCF-5 antisense FGFR1 Smads

项目摘要

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 … More 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

Smad蛋白家族介导TGF-β超家族的信号转导。为了确定Smad蛋白的作用，使用人真皮成纤维细胞进行体外I型胶原凝胶收缩测定。将在巨细胞病毒启动子下携带小鼠Samd 3、Smad 7或lacZ cDNA的重组E-1缺失腺病毒载体感染到人真皮成纤维细胞中。Smad 3过表达增强胶原凝胶收缩成纤维细胞相比，成纤维细胞过表达的控制lacZ。相反，TGF-β介导的胶原凝胶收缩被成纤维细胞中Smad 7的过表达所抑制。此外，IFN-γ不能拮抗瘢痕疙瘩来源的成纤维细胞包埋的胶原凝胶的收缩活性。毛发周期由多种分子调节，其中FGF-5已被证明促进从生长期到退化期的转变。FGFR-1是FGF-5的一种跨膜受体，定位于细胞膜， ...更多信息毛囊乳头。为了将靶向FGFR-1的反义寡核苷酸应用于治疗脱发，我们在无血清器官培养系统中检测了寡核苷酸对毛囊生长的影响。取C_3H/He小鼠的触须毛囊，在31℃、95%O_2 - 5%CO_2条件下培养72 h。通过预测FGFR-1 mRNA的有效靶位点，制备了20-mer反义核苷酸及其随机排列的对应物。通过在与AlamarBlue染料孵育后测量培养基的荧光强度（FI）来估计毛球中的细胞活性。向培养基中加入30 μM硫代磷酸酯形式的反义寡核苷酸，使FI增加30%，而对照没有产生可检测的变化。然而，与对照组相比，两种寡核苷酸均未显示毛干的进一步延长。这些结果表明FGFR- 1反义核苷酸作为治疗秃头的临床效用。酮康唑（Ketoconazole，KCZ）是一种咪唑类抗真菌剂，在治疗脂溢性皮炎和头皮屑的局部应用中也是有效的。与赋形剂组相比，将2%KCZ局部应用于C3 H/He小鼠的背部皮肤对毛发生长具有宏观上显著的刺激作用（p<0.01，n=10），表明酮康唑可用作毛发生长刺激剂。少