| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Research Abstract |
Epidermal keratinocytes form a cornified cell envelope beneath the plasma membrane during the late stages of differentiation. In psoriasis, the expression pattern of the precursor proteins is known to be deranged ; involucrin expression is increased and loricrin expression is decreased. Using light and electron microscopic immunohistochemistry, we compared normal and psoriatic cornified cell envelope formation. In normal epidermis.cornified cell envelopes were observed from the deepest cornified cells or when present, from the transitional cells, increasing in thickness and changing electron densities with maturation. In psoriatic epidermis, cornified cell envelope formation started earlier, one to several cells below the cornified layr. The normal cornified cell envelope was shown to be involucrin positive only at a very early stage, whereas psoriatic cornified cell envelope showed persistent involucrin immunoreactivity. The results suggest that in normal skin, involucrin is the major
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constituent of the cornified cell envelope only in its early stages of assembly. In contrast, cornified cell envelope formation seems to be initiated prematurely in psoriatic skin, were involucrin remains the major constituent of the cornified cell envelope during maturation.
Transcriptional enhancer factor 1 (TEF-1), which binds to SV40 enhancer, is a nuclear protein expressed in various cells including keratinocytes. TEF-1 protein was shown to be highly expressed on the basal cell layr. We analyzed involucrin promoter activity of the INV-CAT vector, which was constructed by connecting the 5' upstream region of involucrin gene to the CAT reporter gene. Co-transfection of TEF-1 expression vector with INV-CAT vector significantly the INV-CAT promoter activity. The repression was also observed by transfection of the GAL4-TEF-1 vector, which was constructed by replacement of the TEF-1 DNA binding domain by the GAL4 activator domain. This suggests that TEF-1-induced repression is due to interference/squelching of a limiting transcriptional intermediary factor that is essential for involucrin expression. TEF-1 dependent-repression of involucrin gene expression might explain the suprabasal involucrin expression in the epidermis.
The concept of epidermal architecture that depends on epidermal turnover time was established. The epidermal architecture is determined, not by a simple proliferative condition, but rather by an epidermal turnover time (that depends both on cell number as well as on the proliferative condition). This is in relation to 'keratinization process' that requires a definite time to be completed. Using the concept, hyperproliferative 'psoriasiform' epidermis and hypoproliferative 'atrophic' epidermis are naturally described. Less
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