| Project/Area Number |
12670837
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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, School of Medicine |
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Principal Investigator |
IKEDA Shigaku Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan., Assistant Professor, 医学部, 講師 (40193198)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Darier disease / Hailey-Hailey disease / ATP2A2 / ATP2C1 / gene expression / quantitative RT-PCR / UVB / cytokines / organ culture / keratinocytes |
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| Research Abstract |
Darier disease (DD)and Hailey-Hailey disease (HHD)are autosomal dominantily inherited skin diseases recently whose causative genes are identified. Both of genes encode the molecules belong to calcium ATPase that sequesters calcium from cytosole to ER or Golgi. DD gene is symbolized as ATP2A2 and HHD gene is symbolized as ATP2C1.In this study, below mentioned facts were identified in 2000 to 2001. (1) More than 40 mutations in ATP2C1 were identified in the patients with HHD, thus it is confirmed that HHD is caused by mutations in ATP2C1. (2) Histopathological changes similar to DD was induced by the addition of inhibitor of sarco-endoplasmic reticulum calcium ATPase type 2 isoform (DD gene product) or antisense oligonucleotides to ATP2A2 in organ culture of normal human skin explants. Because ATP2A2 hemi-knock out mice did not show any specific skin changes similar to that of DD, so far this organ culture system seems to be only an experimental model for DD. (3) Expression of ATP2A2 and ATP2C1 was spontaneously suppressed by irradiation of UVB (50ml/cm2) in cultured normal human keratinocyted. (4) Increase in extracellular calcium concentration form low (0.03mM) to high (1.8mM) spontaneously stimulated the expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes. (5) Addition of IL-6 to the culture media down-regulated the expression of both genes in cultured normal human keratinocytes.
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