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Establishment of a system in which type VII collagen and laminin 5 or their genes are continuously delivered from the dermal side to the basement membrane zone

Research Project

Project/Area Number 15390337
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

SAWAMURA Daisuke  Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (60196334)

Co-Investigator(Kenkyū-buntansha) TABATA Yasuhiko  Kyoto University, Frontier Medical Sciences, Prof., 再生医科学研究所, 教授 (50211371)
TAKAGAKI Keiichi  Hirosaki Univ., School of Med., Prof., 医学部, 教授 (70163160)
SHIMIZU Hiroshi  Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (00146672)
AKIYAMA Masashi  Hokkaido University Hospital, Lec., 病院・講師 (60222551)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2004: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2003: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsepidermolysis bullosa / dystrophic / severe / type VII collagen / laminin 5 / protein therapy / gene transfer / dermis
Research Abstract

Epidermolysis bullosa is caused by mutations in the genes encoding structural proteins of basement membrane zone. Especially, the subtypes resulting from type VII collagen and laminin 5 genes showed severe phenotype and low quality of life. These structural proteins are thought to be produced by epidermal keratinocytes. Many dermatological investigators intend to introduce the causative genes to keratinocytes and to supply those gene products to basement membrane. The aim of this study was to establish a system in which type VII collagen and laminin 5 or their genes were continuously delivered from the dermal side to the basement membrane zone. We succeeded in purification of a large amount of recombinant type VII collagen last year. The injection of the protein induced deposition of type VII collagen in the basement membrane zone. Also injection of gene-transferred fibroblasts enabled type VII collagen to go into the basement membrane. Furthermore, implantation of these fibroblasts in scaffold increased the amount of type VII collagen in the basement membrane zone. Thus, we think that we can achieve establishment of the system in which type VII collagen and laminin 5 or their genes are continuously delivered from the dermal side to the basement membrane zone.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (29 results)

All 2005 2004 Other

All Journal Article (20 results) Publications (9 results)

  • [Journal Article] Keratotic lesions in epidermolysis bullosa simplex with mottled pigmentation.2005

    • Author(s)
      Yasukawa K, et al.
    • Journal Title

      J Am Acad Dermatol 52

      Pages: 172-173

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] The G2028R glycine substitution mutation in COL7A1 leads to marked inter-familiar clinical heterogeneity in dominant dystrophic epidermolysis bullosa.2004

    • Author(s)
      Nakamura H, et al.
    • Journal Title

      J Dermatol Sci 34

      Pages: 195-200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vivo transfer of TGF-alpha and beta genes to keratinocytes.2004

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      J Dermatol Sci 34

      Pages: 234-236

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The G2028R glycine substitution mutation in COL7A1 leads to marked inter-familiar clinical heterogeity in dominant dystrophic epidermolysis bullosa.2004

    • Author(s)
      Nakamura H, et al.
    • Journal Title

      J Dermaol Sci 34

      Pages: 195-200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] In vivo transfer of TGF-alpha and beta genes to keratinocytes.2004

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      J Dermaol Sci 34

      Pages: 234-236

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Mutations in the Plectin Gene (PLEC1) Cause a Novel Clinical Subtype, Epidermolysis Bullosa Simplex Associated with Pyloric Atresia.

    • Author(s)
      Nakamura H, et al.
    • Journal Title

      J Mol Diagn (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Direct injection of plasmid DNA into the skin induces dermatitis by activation of monocytes through toll-like receptor 9.

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      J.Gene Med (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection.

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      Gene Therapy (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical heterogeneity of 1649delG mutation in the tail domain of keratin 5 : a Japanese family with epidermolysis bullosa simplex with mottled pigmentation.

    • Author(s)
      Horiguchi Y, et al.
    • Journal Title

      J Invest Dermatol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Keratinocyte-specific modulation of type VII collagen gene expression by pro-inflammatory cytokines (tumor necrosis factor- and interleukin-1).

    • Author(s)
      Takeda H, et al.
    • Journal Title

      Exp Dermatol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epidermolysis bullosa simplex in Oriental ; genetic studies in 19 patients

    • Author(s)
      Yasukawa K, et al.
    • Journal Title

      Br J Dermatol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutations in the Plectin Gene (PLEC1) Cause a Novel Clincal Subtype, Epidermolysis Bullosa Simplex Associated with Pyloric Atresia.

    • Author(s)
      Nakamura H, et al.
    • Journal Title

      J Mol Diagn (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Direct injection of plasmid DNA into the skin induces dermatitis by activation of monocytes through toll-like receptor 9.

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      J.Gene Med (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection.

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      Gene Therapy (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical heterogeneity of 1649delG mutation in the tail domain of keratin 5 : a Japanese family with epidermolysis bullosa simplex with mottled pigmentation.

    • Author(s)
      Horiguchi Y, et al.
    • Journal Title

      J Invest Dermatol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Keratinocyte-specific modulation of type VII collagen gene expression by pro-inflammatory cytokines (tumor necrosis factor and interleukin-1).

    • Author(s)
      Takeda H, et al.
    • Journal Title

      Exp Dermatol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epidermolysis bullosa simplex in Oriental ; genetic studies in 19 patients.

    • Author(s)
      Yasukawa K, et al.
    • Journal Title

      Br J Dermatol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutations in the Plectin Gene(PLEC1) Cause a Novel Clincal Subtype, Epidermolysis Bullosa Simplex Associated with Pyloric Atresia.

    • Author(s)
      Nakamura H, et al.
    • Journal Title

      J Mol Diagn (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Direct injection of plasmid DNA into the skin induces dermatitis by activation of monocytes through toll-like receptor 9.

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      J.Gene Med (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection.

    • Author(s)
      Sawamura D, et al.
    • Journal Title

      Gene Therapy (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Kawasaki H, et al.: "Squamous cell carcinoma developed in a 12-year-old boy with non-Hallopeau-Siemens recessive dystrophic epidermolysis bullosa"Br J Dermatol. 148. 1047-1050 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sawamura D, et al.: "Epidermolysis bullosa : directions for future research and new challenges for treatment"Arch Dermatol Res. 295. S34-S42 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akiyama M, et al.: "Disruption of suprabasal keratin network by mutation M150T in the helix initiation motif of keratin 10 does not affect cornified cell envelope formation in human epidermis"Exp Dermatol. 12. 628-645 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuzaki Y, et al.: "Keratinocyte responsive element 3 : anaylsis of a keratinocyte-specific regulatory sequence in the 230 kDa bullous pemhigoid antigen promoter"J Invest Dermatol. 120. 308-312 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sawamura D, et al.: "Identification of COL7A1 alternative splicing inserting 9 amino acid residues into the fibronectin type III linker domain"J Invest Dermatol. 120. 942-948 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato-Matsumura KC, et al.: "A novel paternal four base pairs insertion and a maternal nonsense point mutation in COL7A1 identified in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa"Acta Dermato-Venereol. 83. 137-138 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akiyama M, et al.: "The clinical spectrum of non bullous congenital ichthyosiform erythroderma and lamellar ichthyosis"Clin Exp Dermatol. 28. 235-240 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akiyama M, et al.: "Truncation of CGI-58 Protein causes malformation of lamellar granules resulting in ichthyosis in Dorfman-Chanarin syndrome"J Invest Dermatol. 121. 1029-1034 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sasaki H, et al.: "A novel Sp1-family-related cis-acting element for transcription of type VII collagen gene(COL7A1)"J Dermaol Sci. 32. 239-242 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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