2000 Fiscal Year Annual Research Report

角化細胞辺縁帯形成機構の細胞生物学的検討

Research Project

Project/Area Number	10470184
Research Institution	ASAHIKAWA MEDICAL COLLEGE
Principal Investigator	山本明美旭川医科大学, 医学部, 講師 (30241441)
Co-Investigator(Kenkyū-buntansha)	加藤英政旭川医科大学, 医学部, 助手 (50292123) 木山博資旭川医科大学, 医学部, 教授 (00192021) 高橋英俊旭川医科大学, 医学部, 講師 (00216748)
Keywords	表皮 / 辺縁帯 / ロリクリン / 核移行シグナル / インボルクリン / ブロフィラグリン / シスタチンA / 角化症
Research Abstract	1ロリクリン角皮症と辺縁帯形成辺縁帯の主成分ロリクリンの遺伝子異常による角化異常症は我々が発見した疾患であるが、本研究の期間中にも新しい家系を発見し(J Dermatol Sci,1999)、これらロリクリン遺伝子変異による角化症を「ロリクリン角皮症」と呼ぶことを提案した(Exp Dermatol,1998,Histol Histopathol,1998,J Dermatol Sci,1998)。ついで、この遺伝子変異から予想される変異蛋白を検出する特異抗体を作成し、その局在を検討したことろ、変異蛋白は辺縁帯には移行せず、顆粒細胞、角質細胞の核に集積していることが明らかになった(J Invest Dermatol,2000)。とりわけ初期には核小体に局在することから、変異ロリクリンは角化細胞の核、核小体機能を障害することにより角化異常をまねくと考えた。 2ブロフィラグリンアミノ末端ドメインの細胞内局在ブロフィラグリンのアミノ末端ドメインは辺縁帯前駆体と考えられていたが、我々は同ドメインが核内移行することを発見した(Lab Invest 1998)。 3インボルクリンとシスタチンAの遺伝子発現調節機構辺縁帯の成分であるインボルクリンとシスタチンAの遺伝子発現調節機構を明らかにした(J Invest Dermatol,1998,J Biol Chem,1998,Biochem,1999,BBRC,2000)。 4辺縁帯形成におけるエビトーブマスキングの証明辺縁帯形成過程にいてデスモゾーム部分でロリクリンの抗原エビトープのマスクキングがおきることを、殊な免疫電顕法を開発することにより証明した(Exp Dermatol,1999)。

Research Products

(28 results)

All Other

All Publications (28 results)

[Publications] Ishida-Yamamoto A: "Translocation of profilaggrin N-terminal domain into keratinocyte nuclei with fragmented DNA in normal human skin and loricrinkeratoderma."Lab Invest. 78. 1245-1253 (1998)
[Publications] Ishida-Yamamoto A: "Structural organization of cornified cell envelopes and alterations in inherited skin disorders."Exp Dermatol. 7. 1-10 (1998)
[Publications] Ishida-Yamamoto A: "Loricrin and Human skin diseases : molecular basis of loricrin keratodermas."Histol Histopathol. 13. 819-826 (1998)
[Publications] Kon A: "Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa."J Invest Dermatol. 111. 534-537 (1998)
[Publications] Ishida-Yamamoto A: "Inherited disorders of epidermal keratinization."J Dermatol Sci. 18. 139-154 (1998)
[Publications] Inoue N: "Expression of neuropsin in the keratinizing epithelial tissue Immunohistochemical analysis of wild-type and nude mice."J Invest Dermatol. 110. 923-931 (1998)
[Publications] Matsuki M: "Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1 (keratinocyte transglutaminase) ."Proc.Natl.Acad.Sci.USA. 95. 1044-1049 (1998)
[Publications] Sasaki Y: "Abnormalities of basal cell keratin in epidermolysis bullosa simplex do not affect the expression patterns of suprabasal keratins and cornified cell envelope proteins."Arch Dermatol Res. 290. 591-597 (1998)
[Publications] Kawagishi N: "Epidermal coll kinotics of pig skin in vivo following UVB irradiation : Apoptosis inducod by UVB"J Dermatol Sci. 18. 43-53 (1998)
[Publications] Takahashi H: "Adenylate cyclases in keratinocytes : FRSK cells express types I, II, III, IV, VI and VIII, and 1,25 (OH) 2D3, retinoic acid and TPA augment forskolin-induced cyclic AMP accumulation in the absence of altered isozyme expression"Arch Dermatol Res. 290. 407-412 (1998)
[Publications] Takahashi H: "The α and η isoforms of protein kinase C stimulate transcription of human involucrin gene."J Invest Dermatol. 110. 218-223 (1998)
[Publications] Tamura T: "Functional alteration of guanine nucleotide binding proteins (Gs and Gi) in psoriatic epidermis."J Dermatol Sci. 17. 61-66 (1998)
[Publications] Fujimoto W: "Anti-epiligrin cicatricial pemphigoid : a case associated with gastric carcinoma and features resembling epidermolysis bullosa acquista"Br J Dermatol. 139. 682-687 (1998)
[Publications] Takahashi H: "Structure and transcriptional regulation of the human cystatin A gene.The 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element-2 site (-272 to -278) on cystatin A gene is critical for TPA-dependent regulation."J Biol Chem. 273. 17375-17380 (1998)
[Publications] Ishida-Yamamoto A: "Antigen retrieval of loricrin epitopes at desmosomal areas of cornified cell envelopes : an immunoelectron microscopic analysis."Exp Dermatol. 8. 402-406 (1999)
[Publications] Ishida-Yamamoto A: "Electron microsoopic in situ DNA nick end-labeling and combination with immunoelectron microscopy"J Histochem Cytochem. 47. 711-717 (1999)
[Publications] Tamai K: "Recurrent COL7A1 mutations in Japanese patients with dystrophic epidermolysis bullosa : positional effects of premature termination codon mutations on clinical severity"J Invest Dermatol. 112. 991-993 (1999)
[Publications] Ishida-Yamamoto A: "Programmed cell death in normal epidermis and loricrin keratoderma.Multiple functions of profilaggrin in keratinization"J Invest Dermatol Symposium Proceedings. 4. 145-149 (1999)
[Publications] Takahashi H: "Interferon-γ-dependent stimulation of human involucrin gene expression : STAT-1 protein activates involucrin promoter activity"Biochem J. 344. 797-802 (1999)
[Publications] Takahashi H: "Loricrin gene mutation in a Japanese patient of Vohwinkel's syndrome"J Dermatol Sci. 19. 44-47 (1999)
[Publications] Takahashi H: "Fas antigen modulates ultraviolet B (UVB)-induced apoptosis of SVHK cells : sequential activation of caspases 8,3, and 1 in the apoptotic process"Exp Cell Res. 249. 291-298 (1999)
[Publications] Ishida-Yamamoto A: "Mutant loricrin is not crosslinked into the cornified cell envelopes but is translocated into the nuclei in loricrin keratoderma"J Invest Dermatol. 115. 1095-1103 (2000)
[Publications] Ishida-Yamamoto A: "A case of erythrokeratodermia variabilis without mutations in connexin31"Br J Dermatol. 143. 1283-1287 (2000)
[Publications] Ishida-Yamamoto A: "Decreased deiminated keratin K1 in psoriatic hyperproliferative epidermis"J Invest Dermatol. 114. 701-705 (2000)
[Publications] Ishida-Yamamoto A: "Immunoeloctron microscopy links molecules and morphology in the studies of korntinization"Eur J Dermatol. 10. 429-435 (2000)
[Publications] Takahashi H: "Copper, zinc-superoxide dismutase protects from ultraviolet B-induced apoptosis in SV40-transformed human keratinocytes : the protection is associated with the increased levels of antioxidant enzyme"J Dermatol Sci. 23. 12-21 (2000)
[Publications] Takahashi H: "Transcriptional factor AP-2γ increases human cystatin A gene transcription of keratinocytes"Biochem Biophys Res Commun. 278. 719-723 (2000)
[Publications] Takahashi H: "Cornified cell envelope formation is distinct from apoptosis in epidermal keratinocytes"J Dermatol Sci. 23. 161-169 (2000)

2000 Fiscal Year Annual Research Report

角化細胞辺縁帯形成機構の細胞生物学的検討

Principal Investigator

山本 明美 旭川医科大学, 医学部, 講師 (30241441)

Research Products

[Publications] Ishida-Yamamoto A: "Translocation of profilaggrin N-terminal domain into keratinocyte nuclei with fragmented DNA in normal human skin and loricrinkeratoderma."Lab Invest. 78. 1245-1253 (1998)

[Publications] Ishida-Yamamoto A: "Structural organization of cornified cell envelopes and alterations in inherited skin disorders."Exp Dermatol. 7. 1-10 (1998)

[Publications] Ishida-Yamamoto A: "Loricrin and Human skin diseases : molecular basis of loricrin keratodermas."Histol Histopathol. 13. 819-826 (1998)

[Publications] Kon A: "Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa."J Invest Dermatol. 111. 534-537 (1998)

[Publications] Ishida-Yamamoto A: "Inherited disorders of epidermal keratinization."J Dermatol Sci. 18. 139-154 (1998)

[Publications] Inoue N: "Expression of neuropsin in the keratinizing epithelial tissue Immunohistochemical analysis of wild-type and nude mice."J Invest Dermatol. 110. 923-931 (1998)

[Publications] Matsuki M: "Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1 (keratinocyte transglutaminase) ."Proc.Natl.Acad.Sci.USA. 95. 1044-1049 (1998)

[Publications] Sasaki Y: "Abnormalities of basal cell keratin in epidermolysis bullosa simplex do not affect the expression patterns of suprabasal keratins and cornified cell envelope proteins."Arch Dermatol Res. 290. 591-597 (1998)

[Publications] Kawagishi N: "Epidermal coll kinotics of pig skin in vivo following UVB irradiation : Apoptosis inducod by UVB"J Dermatol Sci. 18. 43-53 (1998)

[Publications] Takahashi H: "Adenylate cyclases in keratinocytes : FRSK cells express types I, II, III, IV, VI and VIII, and 1,25 (OH) 2D3, retinoic acid and TPA augment forskolin-induced cyclic AMP accumulation in the absence of altered isozyme expression"Arch Dermatol Res. 290. 407-412 (1998)

[Publications] Takahashi H: "The α and η isoforms of protein kinase C stimulate transcription of human involucrin gene."J Invest Dermatol. 110. 218-223 (1998)

[Publications] Tamura T: "Functional alteration of guanine nucleotide binding proteins (Gs and Gi) in psoriatic epidermis."J Dermatol Sci. 17. 61-66 (1998)

[Publications] Fujimoto W: "Anti-epiligrin cicatricial pemphigoid : a case associated with gastric carcinoma and features resembling epidermolysis bullosa acquista"Br J Dermatol. 139. 682-687 (1998)

[Publications] Takahashi H: "Structure and transcriptional regulation of the human cystatin A gene.The 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element-2 site (-272 to -278) on cystatin A gene is critical for TPA-dependent regulation."J Biol Chem. 273. 17375-17380 (1998)

[Publications] Ishida-Yamamoto A: "Antigen retrieval of loricrin epitopes at desmosomal areas of cornified cell envelopes : an immunoelectron microscopic analysis."Exp Dermatol. 8. 402-406 (1999)

[Publications] Ishida-Yamamoto A: "Electron microsoopic in situ DNA nick end-labeling and combination with immunoelectron microscopy"J Histochem Cytochem. 47. 711-717 (1999)

[Publications] Tamai K: "Recurrent COL7A1 mutations in Japanese patients with dystrophic epidermolysis bullosa : positional effects of premature termination codon mutations on clinical severity"J Invest Dermatol. 112. 991-993 (1999)

[Publications] Ishida-Yamamoto A: "Programmed cell death in normal epidermis and loricrin keratoderma.Multiple functions of profilaggrin in keratinization"J Invest Dermatol Symposium Proceedings. 4. 145-149 (1999)

[Publications] Takahashi H: "Interferon-γ-dependent stimulation of human involucrin gene expression : STAT-1 protein activates involucrin promoter activity"Biochem J. 344. 797-802 (1999)

[Publications] Takahashi H: "Loricrin gene mutation in a Japanese patient of Vohwinkel's syndrome"J Dermatol Sci. 19. 44-47 (1999)

[Publications] Takahashi H: "Fas antigen modulates ultraviolet B (UVB)-induced apoptosis of SVHK cells : sequential activation of caspases 8,3, and 1 in the apoptotic process"Exp Cell Res. 249. 291-298 (1999)

[Publications] Ishida-Yamamoto A: "Mutant loricrin is not crosslinked into the cornified cell envelopes but is translocated into the nuclei in loricrin keratoderma"J Invest Dermatol. 115. 1095-1103 (2000)

[Publications] Ishida-Yamamoto A: "A case of erythrokeratodermia variabilis without mutations in connexin31"Br J Dermatol. 143. 1283-1287 (2000)

[Publications] Ishida-Yamamoto A: "Decreased deiminated keratin K1 in psoriatic hyperproliferative epidermis"J Invest Dermatol. 114. 701-705 (2000)

[Publications] Ishida-Yamamoto A: "Immunoeloctron microscopy links molecules and morphology in the studies of korntinization"Eur J Dermatol. 10. 429-435 (2000)

[Publications] Takahashi H: "Copper, zinc-superoxide dismutase protects from ultraviolet B-induced apoptosis in SV40-transformed human keratinocytes : the protection is associated with the increased levels of antioxidant enzyme"J Dermatol Sci. 23. 12-21 (2000)

[Publications] Takahashi H: "Transcriptional factor AP-2γ increases human cystatin A gene transcription of keratinocytes"Biochem Biophys Res Commun. 278. 719-723 (2000)

[Publications] Takahashi H: "Cornified cell envelope formation is distinct from apoptosis in epidermal keratinocytes"J Dermatol Sci. 23. 161-169 (2000)

山本明美旭川医科大学, 医学部, 講師 (30241441)