| Project/Area Number |
11670845
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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 | Kyoto Prefectural 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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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Epidermis / Terminal differentiation / Gene expression / Signaling / Pathophysiology / Keratinization / Transglutaminase / 角化細胞 / 創傷治癒 / トランスグルタミナーゼ / ノックアウトマウス |
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| Research Abstract |
Transglutaminase 1 (TGase 1) is a keratinization specific enzyme which catalyzes epsilon-(gamma-glutamyl) lysine cross-linking of substrate proteins to generate the cornified envelope at the cell periphery of the stratum corneum. We examined conjunctiva covering cornea in five eyes in the chronic cicatricial phase of Stevens-Johnson syndrome. In situ hybridization revealed transglutaminase 1 (keratinocyte transglutaminase) mRNA in suprabasal cells of the abnormally thickened corjunctival epithelium in all Stevens-Johnson syndrome patients. In contrast, no message was detected in normal conjunctival or corneal epithelia. We speculate that in Stevens-Johnson syndrome, epithelial hyperproliferation, and transglutaminase 1 gene expression lead to the pathological keratinization of ocular surface mucosal epithelia.
We have shown that disruption of the TGase 1 gene in mice results in neonatal lethality, absence of the cornified envelope, and impaired skin barrier function. Based on the importance of TGase 1 in epidermal morphogenesis, we have now assessed its role in wound healing. In neonatal mouse skin, TGase 1 mRNA as well as keratin 6alpha was induced in the epidermis at the wound edges as early as 2 hours after injury and that expression continued in the migrating enidermis until completion of re-epithelialization. The TGase 1 enzyme co-localized on the plasma membrane of migrating keratinocytes with involucrin, but not with loricrin, which suggests the premature assembly of the cornified envelope. Similar injuries to TGase 1 knockout mouse skins grafted on athymic nude mice showed substantial delays in wound healing concomitant with sustained K6alpha mRNA induction. From these results, we suggest that activation of the TGase 1gene is essential for facilitated repair of skin injury.
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