MELANOCYTE MIGRATION AND REPIGMENTAION OF VITILIGO AND GREY HAIR-REGULATING MECHANISMS OF MELANOCYTE MIGRATION IN EPIDERMIAL-FOLLICULAR UNIT-

表皮毛囊单位黑素细胞迁移及白癜风和白发的色素沉着调节机制

• 批准号: 12670821
• 负责人: HORIKAWA Tatsuya
• 金额: $ 1.28万
• 依托单位: KOBE UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670821/
• 关键词: melanocyte; vitiligo; hair follicle; migration; Dok-1; SHP-2; IL-12; melanoma; 治療; 紫外線; 毛嚢; tyrosinase; IL-12; 白皮症

We showed that SHP-2, a tyrosine phosphatase, plays an important role in cell locomotion, using dominant negative mutant.(Oncogene, 19:75-84,2000). We also found that Dok-1, a docking protein, plays an important role in the movement of B-16 melanoma cells (Mol Cell Biol, 21:5437-5446, 2001). We showed that IL-18 synergistically induces tumor rejection with IL-12 which is locally secreted by IL-12 transfected B-16 melanoma cells in vivo (Cancer Invest, 18;206-13, 2000). Using IL-12 transfected melanoma cells, we showed that CD4+T cell depletion induces both melanoma rejection and vitiligo-like depigmentation (J Invest Dermatol, 115:1059-1064,2000). In this regards, we found that IL-12 restores UV-induced suppression of resposiveness of Tlymphocytes (J Derm Sci, 24:190-202,2000). We also reported that giant melanosomes in Hermansky Pudlak syndrome which has a freature of impaired transportation of melanogenic enzymes in pigment cells (Br J Dermatol, 143:635-640,2000). Further, we showed that rab3A, an important G protein for intracellutar vgesicular transportation, is associated with melanosomes in pigment cells (Pigment Cell Res, 13:332-336,2000). Our findings will provide a useful information in establishing a new strategy of the treatment for depigmented disorders.

我们利用显性失活突变体证明了SHP-2（一种酪氨酸磷酸酶）在细胞运动中发挥重要作用。（Oncogene，19：75-84，2000）。我们还发现Dok-1（一种对接蛋白）在B-16黑色素瘤细胞的运动中发挥着重要作用（Mol Cell Biol, 21:5437-5446, 2001）。我们表明，IL-18 与 IL-12 协同诱导肿瘤排斥，IL-12 是由 IL-12 转染的 B-16 黑色素瘤细胞在体内局部分泌的（Cancer Invest，18；206-13，2000）。使用IL-12转染的黑色素瘤细胞，我们表明CD4+T细胞耗竭诱导黑色素瘤排斥和白癜风样脱色(J Invest Dermatol，115：1059-1064，2000)。在这方面，我们发现IL-12恢复UV诱导的T淋巴细胞反应性抑制(J Derm Sci，24：190-202，2000)。我们还报道了赫曼斯基普德拉克综合征中的巨大黑素体，其具有色素细胞中黑素生成酶运输受损的特征(Br J Dermatol，143：635-640，2000)。此外，我们表明rab3A（细胞内血管运输的重要G蛋白）与色素细胞中的黑素体相关（Pigment Cell Res，13：332-336，2000）。我们的研究结果将为建立治疗色素脱失性疾病的新策略提供有用的信息。

项目成果

Horikawa T et al.: "Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes"Br J Dermatol. 143. 635-640 (2000)

Horikawa T 等人：“Hermansky-Pudlak 综合征伴巨大黑素体的杂合 HPS1 突变”Br J Dermatol。

Arakik: "Small GTPase Rab3A is associated with melanosomes in melanoma cells"Pigment Cell Res. 13. 332-366 (2000)

Arakik：“小 GTP 酶 Rab3A 与黑色素瘤细胞中的黑色素体相关”Pigment Cell Res。

Hosooka T, Noguchi T, Nagai H, Horikawa T, Matozaki T, Ichihashi M, Kasuga M: "Inhibition of the motility and growth of B16F10 mouse melanoma cells by dominant negative mutant of Dok-1"Mol Cell Biol. 21. 5437-5446 (2001)

Hosooka T、Noguchi T、Nagai H、Horikawa T、Matozaki T、Ichihashi M、Kasuga M：“Dok-1 显性失活突变体对 B16F10 小鼠黑色素瘤细胞的运动和生长的抑制”Mol Cell Biol。

Horikawa T: "Heterozygous HPS 1 mutation in case of Hermansky-Pudlak syndrome with giant melanosomes"Br.J Dermatol. 143. 635-640 (2000)

Horikawa T：“Hermansky-Pudlak 综合征伴巨大黑素体的杂合 HPS 1 突变”Br.J Dermatol。

Nagai H: "Elimination of CD4+T cells enhances antitumor effect of locally secreted interleukin-12 on B16 melanoma and induces vitiligo-like coat color alteration."J.Invest Dermatol. 115. 1059-1064 (2000)

Nagai H：“消除 CD4 T 细胞可增强局部分泌的白细胞介素 12 对 B16 黑色素瘤的抗肿瘤作用，并诱导白癜风样皮毛颜色改变。”J.Invest Dermatol。