Study of hair growth mechanism through ABS transporter and adenosine

通过ABS转运蛋白和腺苷研究毛发生长机制

• 批准号: 15591179
• 负责人: ARASE Seiji
• 金额: $ 2.24万
• 依托单位: The University of Tokushima
• 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-15591179/
• 关键词: K channel opener; adenosine; adenosine receptor type 2; VEGF; FGF-7; Ephrin A3; BMP2; hair growth; 発毛剤; ミノキシジール; K-チャネル; スルフォニルウレア受容体; ABCトランスポータ

We have reported the mechanism by which minoxidil, (MXD), an ATP dependent K channel opener, promotes hair growth. MXD up-regulates expression of VEGF mRNA in dermal papillae cells(DPCs) through adenosine(Ad) and its receptors(AdRs) pathway, and secreted VEGF finally stimulates hair growth. Ad plays various physiological functions such as cAMP regulation resulting in possible activation of DPCs. So we studied other biological function of Ad in DPCs using DNA microarray analysis which revealed pronounced up-regulation of FGF-7 mRNA expression in the DPCs treated with Ad. A quantitative analysis using real time RT-PC, specific antagonists to each AdRs, immunohistochemical methods, suggest that Ad stimulated FGF-7 mRNA expression via AdoR 2b in DPCs. FGF-7 expressed in DP cells and its receptor FGFr2 expressed in the entire follicular keratinocytes play a critical role in the control of hair growth^2. Taken all together, we concluded that Ad might activate hair growth by the stimulation of FGF-7 expression in DPCs. Based on these studies we have developed a new hair growth stimulating product which is now available to purchase[2].We also studied the difference in the gene expression profile of DPCs from the skin of androgenetic alopecia(AGA) and normal part using DNA microarray analysis. A marked difference was observed in the decreased gene expression of BMP2 and ephrin A3 among 1185 analyzed genes. In order to clarify the roles of BMP2 and ephrin A3 in the hair follicles, we examined the effect of BMP2 and ephrin A3 on the proliferation of hair follicle keratinocyte, and found that both BMP2 and ephrin A3 raised the proliferation rate of the outer root sheath cells (ORSCs). These results lead us to the hypothesis that both BMP2 and ephrin A3 function as hair growth promoting factors in the hair cycle[1].

我们报道了米诺地尔 (MXD)（一种 ATP 依赖性 K 通道开放剂）促进毛发生长的机制。 MXD通过腺苷(Ad)及其受体(AdRs)途径上调真皮乳头细胞(DPCs)中VEGF mRNA的表达，分泌VEGF最终刺激毛发生长。 Ad 发挥多种生理功能，例如 cAMP 调节，可能导致 DPC 激活。因此，我们使用 DNA 微阵列分析研究了 Ad 在 DPC 中的其他生物学功能，结果显示用 Ad 处理的 DPC 中 FGF-7 mRNA 表达显着上调。使用实时 RT-PC、每种 AdR 的特异性拮抗剂、免疫组织化学方法进行的定量分析表明，Ad 通过 AdoR 2b 在 DPC 中刺激 FGF-7 mRNA 表达。 DP细胞中表达的FGF-7及其整个毛囊角质形成细胞中表达的受体FGFr2在控制毛发生长^2中发挥着关键作用。综上所述，我们得出结论，Ad 可能通过刺激 DPC 中的 FGF-7 表达来激活毛发生长。基于这些研究，我们开发了一种新的毛发生长刺激产品，现已可供购买[2]。我们还利用 DNA 微阵列分析研究了雄激素性脱发 (AGA) 皮肤和正常部位皮肤中 DPC 基因表达谱的差异。在 1185 个分析基因中，BMP2 和 ephrin A3 的基因表达降低存在显着差异。为了阐明BMP2和ephrin A3在毛囊中的作用，我们检测了BMP2和ephrin A3对毛囊角质形成细胞增殖的影响，发现BMP2和ephrin A3均提高了外根鞘细胞（ORSC）的增殖率。这些结果使我们得出这样的假设：BMP2 和肝配蛋白 A3 都在毛发周期中充当毛发生长促进因子 [1]。

项目成果

Oura H, Bertoncini J, Detmar M. et al.: "A critical role of placental growth factor in the induction of inflammation and edema formation"Blood. 101(2). 560-567 (2003)

Oura H、Bertoncini J、Detmar M. 等人：“胎盘生长因子在诱导炎症和水肿形成中的关键作用”血液。

Different gene expression profile observed in dermal papilla cells related to androgenic alopecia by DNA microarray analysis.

通过 DNA 微阵列分析，在与雄激素性脱发相关的真皮乳头细胞中观察到不同的基因表达谱。

• 发表时间: 2004
• 期刊: J Dermatol Sci. 36
• 作者: Midorikawa T;et al.
• 通讯作者: et al.

Takishita E, Takahashi A, Nakaya Y. et al.: "Effect of sarpogrelate hydrochloride, a 5-HT2 blocker, on insulin resistance in Otsuka Long-Evans Tokushima fatty rats(OLETF rats), a type 2 diabetic rat model"J Cardiovasc Pharmacol. 43(2). 266-270 (2004)

Takishita E、Takahashi A、Nakaya Y. 等人：“盐酸沙格雷酯（5-HT2 阻滞剂）对 2 型糖尿病大鼠模型大冢 Long-Evans 德岛脂肪大鼠 (OLETF 大鼠) 胰岛素抵抗的影响”J Cardiovasc

Shikiji T, Oura H, Arase S, et al.: "Keratinocytes can differentiate into eccrine sweat ducts in vitro : involvement of epidermal growth factor and fetal bovine serum"J Dermatol Sci.. 33(3). 141-150 (2003)

Shikiji T、Oura H、Arase S 等人：“角质形成细胞可在体外分化为小汗腺导管：表皮生长因子和胎牛血清的参与”J Dermatol Sci.. 33(3)。

Nakamura Y, Arase S, Kido H. et al.: "Cloning, expression analysis, and tissue distribution of esp-1/testisin, a membrane-type serine protease from the rat"J Med Invest. 50(2). 78-86 (2003)

Nakamura Y、Arase S、Kido H. 等人：“esp-1/testisin（一种来自大鼠的膜型丝氨酸蛋白酶）的克隆、表达分析和组织分布”J Med Invest。