| Co-Investigator(Kenkyū-buntansha) |
KATO Hidemasa Department of Anatomy ASAHIKAWA MEDICAL COLLEGE, Assistant Professor, 医学部, 助手 (50292123)
KIYAMA Hiroshi Department of Anatomy ASAHIKAWA MEDICAL COLLEGE, Professor, 医学部, 教授 (00192021)
TAKAHASHI Hidetoshi Department of Dermatology ASAHIKAWA MEDICAL COLLEGE, Assistant Professor, 医学部, 講師 (00216748)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
1. Loricrin keratoderma and cornified cell envelope formation
Loricrin is the major constituent of cornified cell envelopes. We have discovered keratinization disorders caused by mutations of the loricrin gene and proposed the term 'loricrin keratoderma' for this unique group of diseases (J Dermatol Sci, 1999, Exp Dermatol, 1998, Histol Histopathol, 1998, J Dermatol Sci, 1998). We also raised antibodies against synthetic peptides corresponding to the mutated sequences of patients' loricrin gene. We have detected mutant loricrin in the nuclei of differentiated epidermal cells in the patient skin. Mutant loricrin was not detected on the cornified cell envelopes. This suggests that mutant loricrin has a dominant negative effect not on cornified cell envelope assembly itself, but on some nuclear functions (J Invest Dermatol, 2000).
2. Subcellular localization of amino-terminal domain of profilaggrin
It has been suggested that amino-terminal domain of profilaggrin functions as a component of cornified cell envelopes. We have, however, detected nuclear localization of this domain in the terminally differentiated keratinocytes (Lab Invest 1998).
3. Regulation of expression of the genes for involucrin and cystatin A
We have revealed regulatory mechanisms for the genes encoding involucrin and cystat in A, both are components of cornified cell envelopes (J Invest Dermatol, 1998, J Bi ol Chem, 1998, Biochem, 1999, BBRC, 2000).
4. Epitope masking in cornified cell envelope formation
We have shown that loricrin epitopes have been masked at the desmosome areas in the matured cornified cell envelopes by developing a new immunoelectron microscopy technique (Exp Dermatol 1999).
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