|Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Immunoelectron microscopic analysis of the process of cornified cell envelope formation in normal epidermis showed that involucrin is cross-linked earlier than loricrin (J Histochem Cytochem, 44 : 167-175,1996). Furthermore, we showed that cornified cell envelopes in psoriatic epidermis without granular layr was rich in involucrin and formed in a premature stage, while psoriatic epidermis with granular layr had envelopes similar to normal (J Histochem Cytochem, 44 : 167-175,1996). We also showed that psoriatic epidermis can be classified into two types ; epidermis with granular layr and without granular layr and these two have different proliferative situation when assessed by morphometry (Br J Dermatol 135 : 433-438,1996. J Invest Dermatol, 109 : 806-810,1997).
We induced expression of involucrin and SPRR in cultured normal human keratinocytes by increasing calcium concentration in the culture medium, and analyzed their localization and ultrastructural changes and showed that involucri
n and SPRR were expressed and incorporated into the cornified cell envelopes in this order (J Invest Dermatol, 108 : 12-16,1997).
When we assessed expression patterns of keratinocytes differentiation-related proteins, we found that profilaggrin and trichohyalin had distinct expression patterns in normal and psoriatic epidermis, tongue epithelia and cultured keratinocytes despite that they have similar gene structures (Br J Dermatol, 137 : 9-16,1997). We further revealed that involucrin gene expression is stimulated by alpha and eta isoforms of protein kinase C (J Invest Dermatol, in press).
We showed that genetic keratinization disorders, Vohwinkel syndrome and progressive symmetric erythrokeratoderma were diseases of loricrin by morphological and molecular genetic studies (Nature Genetics, 13 : 70-77,1996. J Invest Dermatol, 109 : 604-610,1997, Am J Hum Genet, 61 : 581-589,1997) and we proposed that these diseases can be called loricrin keratoderma (Histol & Histopath, in press. Exp Dermatol, in press).
In the analysis of cornified cell envelope formation, disribution of envelope precursor protein, and morphology and function of epidermis in knockout mice for the transglutaminase 1 gene, it was found that cornified cell envelope formation, and distribution and cross-linking of loricrin and profilaggrin were disrupted, barrier function of the epidermis was severely decreased and mice died soon after birth (PNAS,in press). Less