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

20051)将ATP21启动子与SP-1或YY-1克隆共转入细胞内，可刺激其表达。2)在HaCat细胞培养中，SP-1的表达随着细胞外钙浓度的升高而上调。3)角质形成细胞中SP-1的表达水平较低，对细胞外钙浓度升高没有反应，这是由于ATP21基因突变导致细胞胞浆内钙浓度异常稳定-高水平所致。结果20061)我们鉴定了-550/-528，-488/-471，2)凝胶移位分析发现Sp-1，而不是Sp-3结合在-550/-528和-488/-471区域。3)siRNA下调Sp-1蛋白，导致培养的正常人角质形成细胞ATP2A2蛋白表达下降，提示控制Sp1的表达可能是治疗HHD和DD的一种候选治疗方法。

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.