2000 年度実績報告書

角化細胞辺縁帯形成機構の細胞生物学的検討

研究課題

研究課題/領域番号	10470184
研究機関	旭川医科大学
研究代表者	山本明美旭川医科大学, 医学部, 講師 (30241441)
研究分担者	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)
キーワード	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
研究概要	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)。

研究成果
(28件)

すべてその他

すべて文献書誌 (28件)

[文献書誌] 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)
[文献書誌] Ishida-Yamamoto A: "Structural organization of cornified cell envelopes and alterations in inherited skin disorders."Exp Dermatol. 7. 1-10 (1998)
[文献書誌] Ishida-Yamamoto A: "Loricrin and Human skin diseases : molecular basis of loricrin keratodermas."Histol Histopathol. 13. 819-826 (1998)
[文献書誌] Kon A: "Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa."J Invest Dermatol. 111. 534-537 (1998)
[文献書誌] Ishida-Yamamoto A: "Inherited disorders of epidermal keratinization."J Dermatol Sci. 18. 139-154 (1998)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Kawagishi N: "Epidermal coll kinotics of pig skin in vivo following UVB irradiation : Apoptosis inducod by UVB"J Dermatol Sci. 18. 43-53 (1998)
[文献書誌] 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)
[文献書誌] Takahashi H: "The α and η isoforms of protein kinase C stimulate transcription of human involucrin gene."J Invest Dermatol. 110. 218-223 (1998)
[文献書誌] Tamura T: "Functional alteration of guanine nucleotide binding proteins (Gs and Gi) in psoriatic epidermis."J Dermatol Sci. 17. 61-66 (1998)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Ishida-Yamamoto A: "Electron microsoopic in situ DNA nick end-labeling and combination with immunoelectron microscopy"J Histochem Cytochem. 47. 711-717 (1999)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Takahashi H: "Interferon-γ-dependent stimulation of human involucrin gene expression : STAT-1 protein activates involucrin promoter activity"Biochem J. 344. 797-802 (1999)
[文献書誌] Takahashi H: "Loricrin gene mutation in a Japanese patient of Vohwinkel's syndrome"J Dermatol Sci. 19. 44-47 (1999)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Ishida-Yamamoto A: "A case of erythrokeratodermia variabilis without mutations in connexin31"Br J Dermatol. 143. 1283-1287 (2000)
[文献書誌] Ishida-Yamamoto A: "Decreased deiminated keratin K1 in psoriatic hyperproliferative epidermis"J Invest Dermatol. 114. 701-705 (2000)
[文献書誌] Ishida-Yamamoto A: "Immunoeloctron microscopy links molecules and morphology in the studies of korntinization"Eur J Dermatol. 10. 429-435 (2000)
[文献書誌] 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)
[文献書誌] Takahashi H: "Transcriptional factor AP-2γ increases human cystatin A gene transcription of keratinocytes"Biochem Biophys Res Commun. 278. 719-723 (2000)
[文献書誌] Takahashi H: "Cornified cell envelope formation is distinct from apoptosis in epidermal keratinocytes"J Dermatol Sci. 23. 161-169 (2000)

2000 年度 実績報告書

角化細胞辺縁帯形成機構の細胞生物学的検討

研究代表者

山本 明美 旭川医科大学, 医学部, 講師 (30241441)

研究成果

[文献書誌] 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)

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

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

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

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

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

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

[文献書誌] 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)

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

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

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] 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)

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

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

[文献書誌] 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)

[文献書誌] 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)

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

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

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

[文献書誌] 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)

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

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

2000 年度実績報告書

山本明美旭川医科大学, 医学部, 講師 (30241441)