Analysis of promoter regions in Hailey-Hailey disease and Darier's disease genes.

Hailey-Hailey 病和 Darier 病基因启动子区域分析。

• 批准号: 15591194
• 负责人: IKEDA Shigaku
• 金额: $ 1.79万
• 依托单位: JUNTENDO 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-15591194/
• 关键词: Hailey-Hailey disease; Darier's disease; gene; promoter; SP-1; YY-1; SP-1

Results obtained by research in 2003.1) We have identified 6 SNPs on the promoter region (from non-cording to -1200bp) of ATP2C1 (Hailey-Hailey disease (HHD) gene). There was no correlation between these SNPs and disease phenotypes of HHD.2) Various segments of promoter region of ATP2C1 were cloned into Luciferase vector, and reporter assay was performed using HaCat cell. We have identified +22 to +60 by segment as a expression controlling element for ATP2C1. Additional gel-sift assay utilizing antibodies and mutant decoy DNA segments revealed that two transcription factors, SP-1 and YY-1, could bind to this promoter region.Results obtained by research in 2004.1) Co-transfection of ATP2C1 promoter and SP-1 or YY-1 clone into the cells stimulated the expression of ATP2C1.2) Expression of SP-1 itself was up regulated by raised extracellular calcium concentration in the culture of HaCat cells.3) Expression of SP-1 was low in HHD keratinocytes and did not respond to raised extracellular calcium concentration in the culture due to abnormally stable-high level of calcium concentration in the cytosole of the cells caused by genetic mutation of ATP2C1.

2003年的研究结果：1）在Hailey-Hailey disease（HHD）基因ATP 2C 1启动子区（从非编码区到-1200bp）发现了6个SNPs。2）将ATP 2C 1基因启动子区的不同片段克隆到荧光素酶载体中，利用HaCat细胞进行报告基因分析。我们已经确定+22至+60片段作为ATP 2C 1的表达控制元件。利用抗体和突变体诱饵DNA片段的另外的凝胶筛选测定揭示了两种转录因子，SP-1和YY-1，2004年的研究结果表明：1）将SP-1或YY-1克隆与ATP 2C 1启动子共转染入细胞，可刺激ATP 2C 1的表达; 3）SP-1在HHD角质形成细胞中的表达较低，并且由于其异常稳定的蛋白质表达而对培养物中升高的细胞外钙浓度没有反应。ATP 2C 1基因突变导致细胞胞浆内钙离子浓度升高。

项目成果

Organotypic culture and surface plantation using umbilical cord epithelial cells : Morphogenesis and expression of differenciation markers mimicking cutaneous epidermis

使用脐带上皮细胞的器官型培养和表面种植：模仿皮肤表皮的形态发生和分化标记物的表达

• 发表时间: 2004
• 期刊: J Dermatol Sci 35
• 作者: Mizoguchi M;Suga Y;Sanmano B;Ikeda S;et al.
• 通讯作者: et al.

Japanese guidelines for diagnosis and treatment of junctional and dystrophic epidermolysis bullosa

• DOI: 10.1007/s00403-002-0379-y
• 发表时间: 2003-04-01
• 期刊: ARCHIVES OF DERMATOLOGICAL RESEARCH
• 影响因子: 3
• 作者: Tamai, K;Hashimoto, I;Ogawa, H
• 通讯作者: Ogawa, H

Recurrent E413K Mutation of hHb6 in a Japanese Family with Monilethrix.

日本念珠菌家族中 hHb6 的复发性 E413K 突变。

• 发表时间: 2003
• 期刊: Dermatology 206
• 作者: Muramatsu S;Kimura T;Ueki R;Ikeda S;et al.
• 通讯作者: et al.

The prognosis of pemphigus patients will be significantly improved in the future.

未来天疱疮患者的预后将会明显改善。

• 发表时间: 2003
• 期刊: Arch Dermatol Res 295
• 作者: Ikeda S;Komiyama E;Ogawa H
• 通讯作者: Ogawa H

Clinical tryal of allogeneic cultured dermal substitute for the treatment of intractable skin ulcers in three patients with recessive dystrophic epidermolysis bullosa.

同种异体培养真皮替代品治疗三例隐性营养不良性大疱性表皮松解症患者顽固性皮肤溃疡的临床试验。

• 发表时间: 2004
• 期刊: J Am Acad Dermatol 50
• 作者: Hasegawa T;Suga Y;Mizoguchi M;Ikeda S;Ogawa H;Kubo K;Matsui H;Kagawa S;Kuroyanagi Y
• 通讯作者: Kuroyanagi Y