Analysis of promoter regions in Hailey-Hailey disease and Darier's disease genes (2^<nd> report)

2005年的研究结果1）ATP 2C 1启动子和SP- 1或YY- 1克隆共转染入细胞刺激ATP 2C 1的表达。2）SP-1本身的表达在HaCat细胞培养物中被升高的细胞外钙浓度上调。3）SP- 1在HHD角质形成细胞中表达低，并且对升高的细胞外钙浓度没有反应。培养物中的细胞钙浓度由于ATP 2C 1基因突变引起的细胞胞浆中钙浓度异常稳定-高水平。2006年研究获得的结果1）我们已经鉴定了-550/-528，-488/-471，2）Sp1，凝胶位移分析发现Sp3与-550/-528和-488/-471区域结合，而Sp3不与之结合。用siRNA敲低Sp1蛋白可导致培养的正常人角质形成细胞中ATP 2A 2蛋白的表达减少，这些结果表明，表达可能是治疗HHD和DD的候选治疗选择。

Results obtained by research in 20051) 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 extra-cellular 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.Results obtained by research in 20061) We have identified -550/-528, -488/-471, -390/1361 and -42/-20 of ATP2A2 as candidate promoter regions by the reporter assay.2) Sp 1, but not Sp3 was found to bind to -550/-528 and -488/-471 regions by gel shift assay.3) Knock down of Sp 1 protein by siRNA resulted in decrease of ATP2A2 protein in cultured normal human keratinocytes.These results implicated that controlling Sp1 expression might likely be a candidate therapeutic option for the treatment of HHD and DD.