| Project/Area Number |
14570794
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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 | Asahikawa Medical College |
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Principal Investigator |
YAMAMOTO Akemi Asahikawa Medical College, Department of Dermatology, Assistant Professor, 医学部, 講師 (30241441)
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| Co-Investigator(Kenkyū-buntansha) |
高橋 英俊 旭川医科大学, 医学部, 講師 (00216748)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Deimination / Serine Protease / Kallikrein / Netherton syndrome / SNARE protein / SNAP29 / Lamellar granules / Dermokin / Netherton症候群 / SNARE / CEDNIK症候群 / グルコシルセラミド / デスモゾーム / カテプシン / デスモグレイン / 角化異常症 / ケラチン / 魚鱗癬 / ロリクリン / インボルクリン / エラフィン / 掌蹠角化症 / 辺縁帯 / 核移行シグナル |
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| Research Abstract |
We studied peptidylarginine deiminases (PADs) expression in human epidermis (Cell Mol Life Sci 2005). We found that PAD1,2 and 3 are expressed. PAD1 and PAD3 are co-localized with filaggrin. PAD was present up to the supper corneocytes where it deiminates keratin K1.
We have shown that LEKI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum in the epidermis (J Invest Dermatol 2005).
We also disclosed that in Netherton syndrome where LEKTI is absent, an abnormal split was seen in the superficial stratum granulosum, suggesting that LEKTI is preventing premature loss of stratum corneum cohesion.
We generated SPINK5-deficient mice as a model for Netherton syndrome. Using this model, we showed that desmosome cleavage due to desmoglein 1 degradation is the primary pathogenic event in this disease. (Nature Genetics 2005).
We describe a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK syndrome) caused by a mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking (Am J Hum Genet 2005). In the ichthyotic patient skin, secretion of lamellar granule proteins was inhibited.
We have identified novel members of lamellar granule proteins, namely A2ML (alpha-2 macroglobulin-like) and Dermokin (J Biol Chem, 2006,J Invest Dermatol 2006).
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