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Molecular function and signaling in regulation of desmosomal adhesion : effects of pemphigus IgG

Research Project

Project/Area Number 13470169
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionGIFU UNIVERSITY

Principal Investigator

KITAJIMA Yasuo  GIFU UNIVERSITY, School of Medicine, Professor, 医学部, 教授 (70111797)

Co-Investigator(Kenkyū-buntansha) ICHIHASHI Naoki  GIFU UNIVERSITY, School of Medicine, Assistant, 医学部附属病院, 助手 (50283304)
ICHIKI Yoshiro  GIFU UNIVERSITY, Univ.Hospital, Lecturer, 医学部附属病院, 講師 (30223093)
TAKAGI Hajime  GIFU UNIVERSITY, School of Medicine, Associate Professor, 医学部, 助教授 (70226752)
IZUMI Tomoko  GIFU UNIVERSITY, School of Medicine, Assistant, 医学部, 助手 (70324291)
ESAKI Chikako  GIFU UNIVERSITY, School of Medicine, Assistant, 医学部附属病院, 助手 (70283306)
永井 美貴 (佐藤 美貴)  岐阜大学, 医学部附属病院, 助手 (80324309)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥10,400,000 (Direct Cost: ¥10,400,000)
KeywordsKeratinocytes / Cell-cell junction / Signal transduction / Desmosome / Pemphigus / Bullous diseases / Desmoglein / plasminogen activator / 自己免疫性水泡症
Research Abstract

Pemphigus (P) is an autoimmune bullous disease caused by disruption of desmosomes due to autoantibodies against desmosomal adhesion molecules, desmoglein 3 (Dsg3) for P vulgaris (PV) or Dsg1 for. P foliaceus (PF). It is yet unknown how blisters are induced after PV-IgG bound to desmogleins. The aim of this study is to elucidate the mechanisms of PV-IgG-induced blistering in terms of outside-in signaling caused by PV-IgG binding and control desmosome adhesion. We have previously showed that PV-IgG causes activation of protein kinase C, mediating the secretion of plasminogen activator (uPA), expression of uPA receptor (uPAR), and phosphorylation of Dsg3 associated with its degradation and dissociation from plakoglobin. In the present study, we revealed the involvement of uPAR in blistering by inhibition experiments using uPAR inhibitors (Gun Exp Dermatol 26: 289-295, 2001), and demonstrated that PV-IgG-binding did not cause steric hindrance of desmosome adhesion (J Invest Dermatol 117: 406, 2001). In addition, we showed that clinical symptoms disappear before the titers of Dsg3-ELISA decreased down to normal range (The 23^<rd> Annual Meeting of Bullous Disease Research Club, 2003). We also presented experimental results on the effects of PV-IgG on the other desmosomal molecules (desmocollins, desmoplakins) (Clin.Exp Dermatol 27 : 684-690, 2002, Arch Dermatol Res 295 : s17-123, 2003), and showed the involvement of acetylcholine receptor function in cell-cell adhesion in keratinocytes (Life Science 72 : 208 1-2085, 2003, Exp Cell Res 2004, in press). Recently, we published new results that PV-IgG and methylprednisoline exhibit reciprocal effects on keratinocytes (J Biol Chem279 : 2132-2146, 2004). Regarding the keratin cytoskeleton and epidermolysis bullosa, we found two new types of mutation and a new clinical type of this diseases caused by a new frame-shift and delayed termination codon mutation (J Dermatol 29 : 136-145, 2002, J Invest Dermatol 121: 482-485, 2003).

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Matsuoka Y, Kitajima Y, et al.: "Transient translocation of hemidesmosomal bullous pemphigoid antigen 1 from cytosol to membrane fractions by 12-o-tetradecanoyl phorbol-13-acetate treatment and Ca^<2+>-switch in a human carcinoma cell line"J Dermatol Sci. 27. 206-214 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asano S, Seishima M, Kitajima Y: "Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line"Cli Exp Dermatol. 26. 289-295 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihashi N, Kitajima Y: "Chemotherapy induces or increases expression of multidrug resistance associated protein in malignant melanoma cells"Br J Dermatol. 144. 745-750 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya H, Oyama Z, Kitajima Y: "'Apocrine' poroma : review of literature and case report"J Cutan Pathol. 28. 101-104 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichiki Y, Kitajima Y, et al.: "An extreme severe case of cutaneous calcinosis with juvenile dermatomyositis, and successful treatment with diltiazem"Br J Dermatol. 144. 894-897 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitajima Y: "Mechanisms of desmosome assembly and disassembly"Cli Exp Dermatol. 27. 684-690 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gu LH, Ichiki Y, Sato M, Kitajima Y: "A novel nonsense mutation at E106 of the 2B rod domain of keratin 14 cases dominant epidermolysis bullosa simplex"J Dermatol. 29. 136-145 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gu LH, Ichiki Y, Kitajima Y: "A berrant expression of p16 and RB protein in eccrine porocarcinoma"J Cutan Pathol. 29. 473-479 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitajima Y: "Current and prospective understanding of clinical classification, pathomechanisms and therapy in pemphigus"Arch Dermatol Res. 295. S17-S23 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nguyen VT, Arredondo J, Chernyavsky AI, Kitajima Y, et al.: "Keratinocyte acetylcholine receptors regulate cell adhesion"Life Science. 72. 2081-2085 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Siegel DH, Ashton GHS, Penagos HG, Kitajima Y, et al.: "Loss of kindlin-1, a human homolog of caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes kindler syndrome"Am J Hum Genet. 73. 174-187 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya M, Ichiki Y, Kamiya H, Yamamoto A, Kitajima Y: "Detection of nonmelanoma skin cancer micrometastases in lymph nodes by using reverse transcriptase-polymerase chain reaction for keratin 19 mRNA"Br J Dermatol. 149. 998-1005 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gu LH, Kim SC, Ichiki Y, Park J, Nagai M, Kitajima Y: "An unusual frameshift and delayed termination codon mutation in keratin 5 cause a novel type of epidermolysis bullosa simplex with migratory circinate erythema"J Invest Dermatol. 121. 482-485 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ban M, Sugie S, Kamiya H, Kitajima Y: "Microcystic adnexal carcinoma with lymh node metastasis"Dermatol. 207. 395-397 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya H, Araki M, Kitajima Y: "Nodular fascitis of the cheek"Eur J Dermatol. 13. 189-191 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya H, Kitajima Y: "Successful use of preserved sclera in five cases of eyelid reconstruction and a detailed report of one representative case"Eur J Dermatol. 13. 267-271 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nguyen VT, Arredondo J, Chernyavsky AI, Kitajima Y, et al.: "Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on keratinocytes"J Biol Chem. 279. 2135-2146 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nguyen VT, Chernyavsky AI, Arredondo J, Kitajima Y, et al.: "Synergistic control of epithelial cell adhesion through muscarinic and nicotinic subtypes of cholinergic receptors"Exp Cell Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ban M, Ichiki Y, Kitajima Y: "An outbreak of eruptive pseudoangiomatosis-like lesions due to mosquito bites : erythema punctatum Higuchi"Dermatol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 北島 康雄: "皮膚疾患最新の治療 2003-2004:分担執筆 角層下膿庖症(P106)"南江堂. 265 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuoka Y, Kitajima Y, et al.: "Transient translocation of henildesniosomal bullous peniphigoid antigen 1 from cytosol to membrane fractions by 12-O-tetradecanoyl phorbol-13-acetate treatment and Ca^<2+> in a human carcinoma cell line."J Dermatol Sci. 27. 206-214 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asano S, Seishima M, Kitajima Y: "Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line."Cli Exp Dermatol. 26. 289-296 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichihashi N, Kitajima Y: "Chemotherapy induces or increases expression of multidrug resistance associated protein in malignant melanoma cells"Br J Dermatol. 144. 745-750 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya H, Oyama Z, Kitajima Y: "'Apocrine' poroma : review of literature and case report."J Cutan Pathol. 28. 101-104 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichiki Y, Kitajima Y, et al.: "An extreme severe case of cutaneous calcinosis with juvenile dermatomyositis, and successful treatment with diltiazem"Br J Dermatol. 144. 894-897 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitajima Y: "Mechanisms of desmosome assembly and disassembly"Cli Exp Dermatol. 27. 136-145 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gu LH, Ichiki Y, Sato M, Kitajima Y: "A novel nonsense mutation at E106 of the 2B rod domain of keratin 14 cases dominant epidermolysis bullosa simplex"J Dermatol. 29. 136-145 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gu LH, Ichiki Y, Kitajima Y: "A berrant expression of p16 and RB protein in eccrine porocarcinoma"J Cutan Pathol. 29. 473-479 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitajima Y: "Current and prospective understanding of clinical classification, pathomechanisms and therapy in pemphigus"Arch Dermatol Res. 295. S17-S23 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nguyen VT, Arredondo J, Chernyavsky AI, Kitajima Y, et al.: "Keratinccyte acetylcholine receptors regulate Cell adhesion"Life Scienc. 72. 2081-2085 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Siegel DH, Ashton GHS, Penagos HG, Kitajima Y, et al.: "Loss of kindlin-1, a human homolog of caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes kindler syndrome"Am J Hum Genet. 73. 174-187 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya M, Ichiki Y, Kamiya H, Yamamoto A, Kitajima Y: "Detection of nonmelanonia skin canser micrometastases in lymph nodes by using reverse transcriptase-polymerase chain reaction for keratin 19 mRNA"Br J Dermatol. 149. 998-1005 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gu LW, Kim SC, Ichiki Y, Park J, Nagai M, Kitajima Y: "An unusual frameshift and delayed termination codon mutation in keratin 5 cause a novel type of epidermolysis bullosa simplex with migratory circinate erythema"J Invest Dermatol. 121. 482-485 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ban M, Sugie S, Kamiya H, Kitajima Y: "Microcystic adnexal carcinoma with lymlh node metastasis"Dermatol. 207. 395-397 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya H, Araki M, Kitajima Y: "Nodular fasciitis of the cheek"Eur J Dermatol. 13. 189-191 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamiya H, Kitajima Y: "Successful use of preserved sclera in five cases of eyelid reconstruction and a detailed report of one representative case"Eur J Dermatol. 13. 267-271 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nguyen VT, Arredondo J, Chemyavsky AL, Kitajima Y, et al.: "Pemphigus vulgaris IgG and methyiprednisolone exhibit reciprocal effects on keratinocytes"J Biol Chem. 279. 2135-2146 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nguyen VT, Chemyavsky Al, Arredondo J, Kitajima Y, et al.: "Synergistic control of epithelial cell adhesion through muscarinic and nicotinic subtypes of cholinergic receptors"Exp Cell Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ban M, Ichiki Y, Kitajima Y: "An outbreak of eruptive pseudoangiomatosis-like lesions due to mosquito bites : erythema punctatum Higuchi"Dermatol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nguyen VT, Chemyavsky AI, Arredondo J, Kitajima Y, et al.: "Synergistic control of epithelial cell adhesion through muscarinic and nicotimic subtypes of cholinergic receptors"Exp Cell Res. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nguyen VT, Anedondo J, Chernyavsky AI, Kitajima Y, et al.: "Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on keratinocytes"J Biol Chem. 279・3. 2135-2146 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nguyen VT, Arredondo J, Chernyavsky AI, Kitajima Y, et al.: "Keratinocyte acetylcholine receptors regulate cell adhesion"Life Sciences. 72. 2081-2085 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitajima Y: "Current and prospective understanding of clinical classification, pathomechanisms and therapy in pemphigus"Arch Dermatol Res. 295. S17-S23 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Gu LH, Kim SC, Ichiki Y, Park J, Nagai M, Kitajima Y: "An unusual frameshift and delayed termination codon mutation in keratin 5 causes a novel type of epidermolysis bullosa simplex with migratory circinate erythema"J Invest Dermatol. 121. 482-485 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 北島 康雄: "先天性表皮水疱症"小児科診療. 66. 123-127 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 北島 康雄: "皮膚疾患最新の治療2003-2004:分担執筆 角層下膿疱症"南江堂. 106 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Gu LH, Ichiki Y, Sato M, Kitajima Y: "A novel nonsense mutation at E106 of the 2B rod domain of keratin 14cases dominant epidermolysis bullosa simplex"J Dermatol. 29. 136-145 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Gu LH, Ichiki Y, Kitajima Y: "A berrant expression of p16 and RB protein in eccrine porocarcinoma"J Cutan Pathol. 29. 473-479 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitajima Y: "Mechanisms of desmosome assembly and disassembly"Clin Exp Dermatol. 27. 684-690 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitajima Y: "Current and prospective understanding of clinical classification, pathomechanisms and therapy in pemphigus"Arch Dermatol Res. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 北島 康雄: "水疱症自己抗体とシグナル伝達"現代医療. 34・8. 1111-1117 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 北島 康雄: "先天性表皮水疱症"小児科診療. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 北島 康雄: "最新皮膚科学大系 6 水疱症 膿疱症:分担執筆 単純型表皮水疱症(p166-177)"中山書店. 274 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asano S, Seishima M, Kitajima Y: "Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-lgG-induced acanthalysis in DJM-l cells a squamous cell carciaoma line"Clin Exp Dermatol. 26. 289-295 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitajima Y: "Current and perspective understandings of pemphigus ; clinical classification,pathomech anisms and therapy"Arch Dermatol Res. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitajima Y: "Mechanisms of desmosome,assembly,disassembly and pemphigus"Clin Exp Dermatol. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 北島 康雄: "天疱瘡と類天疱瘡:ケラチノサイト細胞生物学のパラダイム"日皮会誌. 111(12). 1772-1774 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北島康雄, 青山裕美: "表皮角化細胞の自己免疫性シグナル伝達病一尋常性天疱瘡"医学のあゆみ. 196(4). 248-249 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuoka Y, Yamada T, Seishima M Hirako Y, Owaribek, Kitajima Y: "Transient translocation of hemidesmosomal bullous pemphigoid antigen 1 from cytosol to membrane fractions by (2-0-tetradecanoyl phorbol-13 acetate treatment and Ca^<24>-switch in a human carcinoma cell line"J Dermatol Sci. 27. 206-214 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北島 康雄(分担): "最新皮膚科学大系"中山書店.

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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