| Project/Area Number |
11557065
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Dermatology
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| Research Institution | Kyoto Prefecture! University of Medicine |
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Principal Investigator |
YAMANISHI Kiyofumi Kyoto Prefectural University of Medicine, Faculty of Medicine, Lecturer, 医学部, 講師 (10182586)
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| Co-Investigator(Kenkyū-buntansha) |
野坂 和人 京都府立医科大学, 医学部, 助教授 (10228314)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | Transglutaminase / Ichthyosis / Cornified envelope / Knockout mice / Stratum corneum lipid / Skin barrier function / ES cells / Gene trageting / 角化症 / 形態形成 / 角質 / 脂質 / 皮膚疾患 / 分子病態 |
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| Research Abstract |
Transglutaminase 1 knockout mice (TGase1^<-/->) showed immature stratum corneum which lacks the cornified envelopes (CE) with defective assembly of loricrin, a major precursor protein of CE. Severely damaged barrier function of TGase1^<-/-> skin was demonstrated by the high level of transepidermal water loss (TEWL), the acceleration of mannitol transport across the skin, and marked diffusion of lucifer yellow into the skin in vivo. The production of the lamellar bodies was observed in TGase1^<-/-> epidermis. However, the intercellular lipids lamellar structure was apparently irregular in TGase1^<-/-> stratum corneum. Therefore, the re-distribution of the lipids was impaired in TGase1^<-/-> skin. Because TGase1^<-/-> neonates die soon after birth, TGase1^<-/-> skins were grafted onto nude mice to assess their maturated skin phenotype. Two weeks after the transplantation, the grafted TGase1^<-/-> epidermis showed acanthosis, hyperkeratosis, and loss of coat hair growth. The TEWL of the grafted TGase1^<-/-> skins was improved to the normal level. These results indicate the remodeling of the epidermis for adaptation to external environments in grafted TGase1^<-/-> skins. In neonatal mice, the TGase1 gene was induced as early as 2h after skin injury and its expression was evident even in the migrating keratinocytes. A skin injury made on the grafted TGase1^<-/-> skins revealed retardation of wound healing in comparison with grafted normal neonatal skins. In conclusion, TGase1 is essential to maintain internal homeostasis not only by arranging distribution of lipid barrier and assembly of cross-linked protein barrier in the stratum corneum, but also by facilitated regeneration of the skin.
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