• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular medicine of autoimmune bullous diseases in terms of the signal transduction to regulate the cell adhesion molecules and cytoskeletons

Research Project

Project/Area Number 10470186
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) AOYAMA Yumi  GIFU UNIVERSITY School of Medicine, Assistant, 医学部, 助手 (90291393)
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)
山田 孝宏  岐阜大学, 医学部・附属病院, 助手 (50324306)
野尻 麻里  岐阜大学, 医学部・附属病院, 助手 (80311702)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥6,700,000 (Direct Cost: ¥6,700,000)
KeywordsKeratinocytes / Cell-cell junction / Signal transduction / Desmosome / Pemphigus / Bullous diseases / Desmoglein / plasminogen activator / 尋常性天庖瘡 / 類天庖瘡 / 自己免疫水疱症
Research Abstract

Pemphigus (P) is an autoimmune bullous disease caused by autoantibodies against desmosomal adhesion molecules, desmoglein 1 (Dsg1) for P foliaceus (PF) or Dsg3 for P vulgaris (PV). The mechanisms how the binding of these antibodies to Dsgs leads to cell-cell detachment are still unknown. Keratinocytes are thought to response to the extracellular signals to control cell-cell and cell-matrix junctions as other cells. In this respect, we have been focusing on the outside-in signaling caused by PV-IgG binding to Dsg3. Through this project, we have obtained the following results. We showed PV-IgG-dependent activation of protein kinase C (PKC) mediating the secretion of plasminogen activator (Arch Dermatol Res 135 : 1556-1557, 1999), expression of plasminogen activator receptor (J Invest Dermatol Symp Proc 4 : 137-144, 1999), PKC-independent phosphorylation of Dsg3 associated with its degradation and dissociation from plakoglobin (Eur J Immunol 29 : 2233-2240, 1999), and the formation of Dsg3-deficient desmosomes (J Invest Dermatol 112 : 67-71, 1999). Furthermore, we showed the formation of Dsg3 aggregation and half-desmosomes before desmosome formation and the binding of PV-IgG to these aggregations caused endocytosis of PV-IgG-Dsg3 immune complexes (Lab Invest 80 : 1583-1592, 2000). We also used clinically Dsg1, 3 ELISA to follow the clinical course of PV and PF (Eur J Dermatol 10 : 18-21, 2000).

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Aoyama Y,Funahashi M, et al: "ELISA for desmoglein 1 is a possible diagnostic tool to determine the prospective severity and initial therapy for pemphigus foliaceus"Eur J Dermatol. 10. 18-21 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato M,Aoyama Y,Kitajima Y: "Assembly pathway of desmoglein 3 to desmosomes and its perturbation by pemphigus rulgarls-IgG in cultured keratinocytes, as revealed by time-lapsed labeling immunoelectron microscopy"Lab Invest. 80. 1583-1592 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhuxiang Nie,Nagata Y, et al: "IgA antibodies of linear IgA bullous dermatosis recognize the 15^<th> collagenous domain of BP 180"J Invest Dermatol. 115. 1164-1166 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitajima Y,Aoyama Y Seishima M: "Transmembrane signaling for adhesive regulation of desmosomes and hemidesmosomes, and cell-cell detachment induced by pemphig us IgG in cultured keratinocytes : Involvement of protein kinase C"J Invest Dermatol Symposium Proceedings. 4. 137-144 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyama Y,Kitajima Y: "Pemphigus vulgaris-IgG causes a rapid deletion of Desmoglein 3 (Dsg3) from the triton-X 100 soluble pools, leading to the formation of Dsg3-deletal desmosomes in a human squamous carcinoma cell line, DJM-1 cells"J Invest Dermatol. 112. 67-71 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyama Y,Owad a MK,Kitajima Y: "A pathogenic autoantibody, pemphigus vulgaris IgG, induces phosphory-lation of desmoglein 3 , and its dissociation from plakoglobin in cultured kerationocytes"Eur J Immunology. 29. 2233-2240 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 北島康雄(分担): "皮膚科専門医Clinical Exercises"医学書院. 125-127 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 北島康雄(分担): "今日の治療指針2000年版-私はこう治療している"医学書院. 709-710 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyama Y, Funahashi M, et al: "ELISA for desmoglein 1 is a possible diagnostic tool to determine the prospective severity and initial therapy for pemphigus foliaceus"European Journal of Dermatology. 10. 18-21 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato M, Aoyama Y, Kitajima Y: "Assembly pathway of desmoglein 3 to desmosomes and its perturbation by pemphigus vulgaris-IgG in cultured keratinocytes, as revealed by time-lapsed labeling immunoelectron microscopy"Laboratory Investigation. 80. 1583-1592 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhuxiang Nie, Nagata Y, et al: "IgA antibodies of linear IgA bullous dermatosis recognize the 15^<th> collagenous domain of BP 180"Journal of Investigative Dermatology. 115. 1164-1166 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitajima Y, Aoyama Y, Seishima M: "Transmembrane signaling for adhesive regulation of desmosomes and hemidesmosomes, and cell-cell detachment induced by pemphigus IgG in cultured keratinocytes : Involvement of protein kinase C"Journal of Investigative Dermatology Symposium Proceedings. 4. 137-144 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyama Y, Kitajima Y: "Pemphigus vulgaris-IgG causes a rapid deletion of Desmoglein 3 (Dsg3) from the triron-X 100 soluble pools, leading to the formation of Dsg3-deleted desmosomes in a human squamous carcinoma cell line, DJM-1 cell"Journal of Investigative Dermatology. 112. 67-71 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyama Y, Owada MK, Kitajima Y: "A pathogenic autoantibody, pemphigus vulgaris IgG, induces phosphorylation of desmoglein 3, and its dissociation from plakoglobin in cultured keratinocytes"European Journal of Immunology. 29. 2233-2240 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoyama Y,Funahashi M, et al: "ELISA for demoglein 1 is a possible diagnostic tool to determine the prospective severity and initial therapy for pemphigus foliaceus"Eur J Dermatol. 10. 18-21 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sato M,Aoyama Y,Kitajima Y: "Assembly pathway of desmoglein 3 to desmosomes and its perturbation by pempigus vulgaris IgG in cultured keratinocytes, as revealed by time-lapsed labeling immunoelectron microscopy"Lab Invest. 80. 1583-1592 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhuxiang Nie,Nagata Y, et al: "IgG antibodies of linear IgA bullous dermatosis recognize the 15^<th> collagenous domain of BP180"J Invest Dermatol. 115. 1164-1166 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitajima Y: "Blistering mechanisms in bullous pemphigoid after binding of antibodies to the antigens"Korean Journal of Investigative Dermatology. 7(2). 78-86 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北島康雄: "自己免疫性表皮下水疱症の病理組織:類天疱瘡、線状IgA水疱症、疱疹状皮膚炎"病理と臨床「特集 炎症性皮膚疾患:その組織像の多彩性と経時的変化」. 18(1). 37-42 (2000)

    • Related Report
      2000 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-尋常性天疱瘡"医学のあゆみ. 196(4). 248-249 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北島康雄(分担): "今日の治療指針2001年版-私はこう治療している"医学書院. 702 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北島康雄: "今日の診断指針【第5版】"医学書院(In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirako Y, Kitajima Y, et al: "Cleavage of BP180, a 180-Kda bullous pemphigoid antigen, yields a 120 Kda collagenous extracellular polypeptide"Journal of Biological Chemistry. 273(16). 9711-9717 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitajima Y, et al: "Trarnsmembrane signaling for adhesive regulation of desmosomes and hemidesmosomes, and cell-cell detachment induced by penphgus IgG incultured keratinocytes: Involvement of protein kinase C"J. Invest. Dermatol, Symposium Proceedings. 4. 137-144 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Seishima M, Kitajima Y, et al: "Phospratiolylcholine-specific phospholipase C, but not phospholipase D, is involved in pemphigus IgG-induced signal transduction"Arch, Dermatol. Res.. 291. 606-613 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aoyama Y, Kitajima Y: "Penplugus vulgaris-IgG causes a rapid depletion of Desmaglein3(Psg3) from the tritorix-loosoluble pools, leading to the formation of Dsg3-deleted desmosomes in a human squamous carcinoma cell line, PJM-1 cells."J. Invest. Dermatol.. 112. 67-71 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aoyama Y, Kitajima Y, et al: "A pathogenic autoantibody, pemphigus vulgaris IgG, induces phosphorylation of desmoglein3, and its dissociation from plakaglobin in cultured keratinocytes"Eur. J. Immunology. 29. 2233-2240 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Satoh S, Kitajima Y, et al: "The time course of the change in antibody tilresin herpes gestations"Br. J. Dermatol.. 140. 119-123 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitajima Y,et al: "Internalization of the 180kDa bullons pemphigoid antigen as lmmune complexes in basal keratinocytes : an important early event in blister formation in bullons pemphig" British Journal of Dermatology. 138. 71-76 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirako Y, Kitajima Y,et al: "Cleavage of BP180 (Type XVII collagen) yields a 120kDa collagenous extracellular polypeptide" Journal of Biological Chemistry. 273(16). 9711-9717 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sato M, Kitajima Y,et al: "Precise ultrastructural localization of in vivo deposited IgG antibodios in fresh perilesional skin of patients with bullous pemphigoid" British Journal of Dermatology. 138. 965-971 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Izumi T, Kitajima Y,et al: "Pemphigus with features of both vulgaris and foliaceus variants,associated with antibodies to 160 and 130 kDa antigens" British Journal of Dermatology. 139. 688-692 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Seishima M, Kitajima Y,et al: "Increased serum soluble Fas,tumor recrosis factor α and interleukin 6 concentrations in generalized pustular psoriasis" Dermatology. 196. 371-372 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aoyama Y, Kitajima Y: "Pemphigus vulgaris-IgG causes a rapid depletion of Desmoglein3(Dsg3) from the tritonX-100 soluble pools,leading to the formation of Dsg3-doleted desmosomes in a human squamaus carcinomd celllius DJM-1 cells" Jounal of Investigative Dermatology. 112. 67-71 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kitajima Yasuo: "Skin : Interface of a Living System" ELSEVIER, 19(199) (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kitajima Yasuo: "皮膚科学TEXT" 南山堂, 8(427) (1998)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi