1997 Fiscal Year Annual Research Report

角化細胞終末分化関連蛋白の発現とその異常

Research Project

Project/Area Number	08670940
Research Institution	ASAHIKAWA MEDICAL COLLEGE
Principal Investigator	山本明美旭川医科大学, 医学部, 講師 (30241441)
Keywords	ロリクリン / 辺縁帯 / Vohwinkel症候群 / 進行性紅色角皮症 / トランスグルタミネース / 角化細胞 / SPRR / インボルクリン
Research Abstract	正常表皮における辺縁帯形成過程の免疫電顕的検討では、インボルクリンが先に架橋され、のちにロリクリンが架橋されることが示唆された(J Histochem Cytochem,44:167-175,1996)。さらに尋常性乾癬表皮の辺縁帯は、顆粒層を欠く場合はインボルクリン主体となり、しかもより早期に形成されるのに対し、顆粒層を有する場合は正常に近くなることがわかった(同上)。乾癬表皮が顆粒層の有無により2つのパターンに分けられ、それぞれの増殖状態がことなることを形態計測からも明かにした(BrJ Dermatol 135:433-438,1996.J Invest Dermatol,109:806-810,1997)。また、培養ヒト角化細胞において、培養液のカルシウム濃度を上昇させることにより、インボルクリンとSPRRの発現を誘導し、それらの局在と微細構造の変化の関連を解析し、両者が段階的に発現し、角層の辺縁帯に架橋されることを示した(J Invest Dermatol,108:12-16,1997)。角化細胞の分化関連蛋白の発現機構の解析では、プロフィラグリンとトリコヒアリンは共通する遺伝子構造をもちながら、全く独立した発現様式をしめすことが正常および乾癬表皮、舌上皮、培養角化細胞における観察から明らかになった(BrJ Dermatol,137:9-16,1997)。またインボルクリン遺伝子の発現がprotein kinase Cのαおよびηアイソフォームにより促進されることをin vitroの系で証明した(J Invest Dermatol,in press)。さらに遺伝性角化異常症であるVohwinkel症候群と進行性紅色角皮症の原因がロリクリン遺伝の変異によるとを、形態的、分子遺伝学的研究により証明し(Nature Genetics,13:70-77,1996.J Invest Dermatol,109:604-610,1997,Am J Hum Genet,61:581-589,1997)、我々はこれらをLoricrin Keratoderma と呼ぶことを提唱した(Histol & Histopath,in press.Exp Dermatol,in press)。 Transglutaminase1のノックアウトマウスにおいて辺縁帯の形成、辺縁帯前駆体蛋白の挙動、表皮の形態および機能への影響を検討したところ、辺縁帯形成は完全に損なわれ、ロリクリンやプロフィラグリンの細胞内分布、辺縁帯への架橋が障害され、皮膚のバリア機能は著しく低下し、マウスは生後早期に死亡することがわかった(PNAS,in press)。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] A.Ishida-Yamamoto: "Immunoelectron microscopic analysis of cornified cell envelope formation in normal and psoriatic epidermis." J Histochem Cytochem. 44. 167-175 (1996)
[Publications] E.Maestrini: "A molecular defect in loricrin,the major component of the cornified cell envelope,underlies Vohwinkel′s syndrome." Nature Genetics. 13. 70-77 (1996)
[Publications] H.Iizuka: "Epidermal remodelling in psoriasis." Br J Dermatol. 135. 433-438 (1996)
[Publications] A.Ishida-Yamamoto: "Eccrin syringofibroadenoma(Mascaro).An ultrastructural and immunohistochemical study." Am J Dermatopathol. 18. 207-211 (1996)
[Publications] A.Ishida-Yamamoto: "Involucrin and SPRR are synthesized sequentially in differentiating cultured epidermal cells." J Invest Dermatol. 108. 12-16 (1997)
[Publications] K.Tamai: "Compound heterozygosity for a nonsense mutation and a splice site mutation in the type VII collagen gene(COL7A1)in recessive dystrophic epidermolysis bullosa." Laboratory Investigation. 76. 209-217 (1997)
[Publications] A,Ishida-Yamamoto: "The molecular pathology of progressive symmetric erythrokeratoderma:a frameshift mutation in the loricrin gene and pertubations in the cornified cell envelope." Am J Hum Genet. 61. 581-589 (1997)
[Publications] A.Isida-Yamamoto: "Distinctive expression of filaggrin and trichohyalin during various pathways of epithelial differentiation" Br J Dermatol. 137. 9-19 (1997)
[Publications] B.P.Korge: "Loricrin mutation in Vohwinkel′s keratoderma is unique to the variant with ichthyosis" J Invest Dermatol. 109. 604-610 (1997)
[Publications] H.Iizuka: "Another support for the location of epidermal stem cells residing adjacent to the tips of dermal papillae in the interfollicular epidermis" J Invest Dermatol. 109. 697 (1997)
[Publications] H.Iizuka: "Epidermal Remodeling in psoriasis(II)" J Invest Dermatol. 109. 806-810 (1997)
[Publications] A.Ishida-Yamamoto: "Loricrin and Human skin diseases:molecular basis of loricrin keratodermas." Histology and Histopathology. (in press).
[Publications] A.Ishida-Yamamoto: "Structural organization of cornified cell envelopes and alterations in inherited skin disorders." Exp Dermatol. (in press).
[Publications] M.Matsuki: "Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1( keratinocyte transglutaminase)." Proc Natl Acad Sci USA. (in press).
[Publications] H.Takahashi: "The α and η isoforms of protein kinase C stimulate transcription of human involucrin gene." J Invest Dermatol. (in press).
[Publications] T.Tamura: "Functional alteration of guanine nucleotide binding proteins(Gs and Gi) in psoriatic epidermis." J Dermatol Sci. (in press).
[Publications] H.Tanaka: "A Novel Variant of Acquired Epidermolysis Bullosa with Autoantibodies against the Central Triple-Helical Domain of Type VII Collagen." Laboratory Investigation. 77. 623-632 (1997)

1997 Fiscal Year Annual Research Report

角化細胞終末分化関連蛋白の発現とその異常

Principal Investigator

山本 明美 旭川医科大学, 医学部, 講師 (30241441)

Research Products

[Publications] A.Ishida-Yamamoto: "Immunoelectron microscopic analysis of cornified cell envelope formation in normal and psoriatic epidermis." J Histochem Cytochem. 44. 167-175 (1996)

[Publications] E.Maestrini: "A molecular defect in loricrin,the major component of the cornified cell envelope,underlies Vohwinkel′s syndrome." Nature Genetics. 13. 70-77 (1996)

[Publications] H.Iizuka: "Epidermal remodelling in psoriasis." Br J Dermatol. 135. 433-438 (1996)

[Publications] A.Ishida-Yamamoto: "Eccrin syringofibroadenoma(Mascaro).An ultrastructural and immunohistochemical study." Am J Dermatopathol. 18. 207-211 (1996)

[Publications] A.Ishida-Yamamoto: "Involucrin and SPRR are synthesized sequentially in differentiating cultured epidermal cells." J Invest Dermatol. 108. 12-16 (1997)

[Publications] K.Tamai: "Compound heterozygosity for a nonsense mutation and a splice site mutation in the type VII collagen gene(COL7A1)in recessive dystrophic epidermolysis bullosa." Laboratory Investigation. 76. 209-217 (1997)

[Publications] A,Ishida-Yamamoto: "The molecular pathology of progressive symmetric erythrokeratoderma:a frameshift mutation in the loricrin gene and pertubations in the cornified cell envelope." Am J Hum Genet. 61. 581-589 (1997)

[Publications] A.Isida-Yamamoto: "Distinctive expression of filaggrin and trichohyalin during various pathways of epithelial differentiation" Br J Dermatol. 137. 9-19 (1997)

[Publications] B.P.Korge: "Loricrin mutation in Vohwinkel′s keratoderma is unique to the variant with ichthyosis" J Invest Dermatol. 109. 604-610 (1997)

[Publications] H.Iizuka: "Another support for the location of epidermal stem cells residing adjacent to the tips of dermal papillae in the interfollicular epidermis" J Invest Dermatol. 109. 697 (1997)

[Publications] H.Iizuka: "Epidermal Remodeling in psoriasis(II)" J Invest Dermatol. 109. 806-810 (1997)

[Publications] A.Ishida-Yamamoto: "Loricrin and Human skin diseases:molecular basis of loricrin keratodermas." Histology and Histopathology. (in press).

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

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

[Publications] H.Takahashi: "The α and η isoforms of protein kinase C stimulate transcription of human involucrin gene." J Invest Dermatol. (in press).

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

[Publications] H.Tanaka: "A Novel Variant of Acquired Epidermolysis Bullosa with Autoantibodies against the Central Triple-Helical Domain of Type VII Collagen." Laboratory Investigation. 77. 623-632 (1997)

山本明美旭川医科大学, 医学部, 講師 (30241441)