2006 Fiscal Year Final Research Report Summary
Analysis of promoter regions in Hailey-Hailey disease and Darier's disease genes (2^<nd> report)
| Project/Area Number |
17591186
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
SHIGAKU Ikeda JUNTENDO UNIVERSITY, School of Medicine, Department of Dermatology, Professor (40193198)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Hailey-Hailey disease / Darier's disease / gene / promoter / SP-1 / YY-1 / Sp3 |
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| Research Abstract |
Results obtained by research in 2005
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 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 2006
1) 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.
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