| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hidetoshi Asahikawa Medical College, Department of Dermatology, Instructor, 医学部, 講師 (00216748)
ISHIDA Akemi (YAMAMOTO Ak) Asahikawa Medical College, Department of Dermatology, Instructor, 医学部, 講師 (30241441)
HASHIMOTO Yoshio Asahikawa Medical College, Department of Dermatology, Associate Professor, 医学部, 助教授 (70172880)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Formation of cornified cell envelope was shown to occur sequentially, initially involving involucrin deposition and subsequently involving SPRR and then loricrin incorporation. Psoriatic epidermis demonstrated a lack of proper cornified cell envelope maturation (Ishida-Yamamoto, Iizuka et al ; J Invest Dermatol 104 : 391-395, 1995 ; Ishida-Yamamoto, Iizuka et al ; J Histochem Cytochem 44 : 167-175, 1996, Ishida-Yamamoto, Iizuka et al ; J Invest Dermatol 108 : 12-16, 1997). Typical psoriatic epidermis has been characterized by a lack of keratohyalin granule, the main constituent of which is profilaggrin. The profilaggrin N-terminal domains were shown to be cleaved from the filaggrin repeats and transiently localized to apoptotic nuclei just before the formation of enucleated stratum corneum (Ishida-Yamamoto, Iizuka ; Lab Invest 78 : 1245-1253,1998).
Psoriatic epidermis has been characterized by decreased beta2-adrenergic response and loricrin. The mRNA levels of beta2-adrenergic receptor
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and loricrin in the involved psoriatic epidermis was shown to be significantly decreased compared with the uninvolved epidermis. In contrast, involucrin mRNA expression of the involved epidermis was significantly increased. These results indicate that the altered expression of the beta2-adrenergic receptor, loricrin and involucrin, in the psoriatic involved epidermis, is associated with different amounts of each mRNA transcript (Takahashi, Iizuka et al ; Br J Dermatol 134 : 1065-1069, 1996).
Among various protein kinase C isozymes in keratinocytes, the alfa and ete isoforms of protein kinase C stimulated transcription of human involucrin gene. (Takahashi, Iizuka et al ; J Invest Dennatol 110 : 218-223, 1998).
Keratolinin was shown to be identical with cystatin A, a cysteine proteinase inhibitor, and its expression was increased in the psoriatic involved epidermis. The 5'-flanking region of the human cystatin A gene was shown to confer promoter activity and contains a TRE that mediates the enhanced expression of this gene by TPA (Takahashi, Iizuka et al ; J Invest Dermatol 108 : 843-847,1997 ; Takahashi, Iizuka et al ; J Biol Chem 273 : 17375-17380,1998) Less
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