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2003 Fiscal Year Final Research Report Summary

Development of a novel therapy for epidermolysis bullosa using recombinant

Research Project

Project/Area Number 13357008
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Dermatology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

SHIMIZU Hiroshi  Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (00146672)

Co-Investigator(Kenkyū-buntansha) FURUICHI Yasuhiro  GeneCare Research Institute Co.Ltd., Manager, 所長(研究職)
SHIMIZU Tadamichi  Hokkaido University, Hospital, Lec., 医学部・歯学部附属病院, 講師 (70260396)
SAWAMURA Daisuke  Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (60196334)
MASUNAGA Takuji  KOSE Corporation, Chief Researcher, 主任研究員
Project Period (FY) 2001 – 2003
KeywordsWound healing / epidermolysis bullosa / dystrophic / severe type / type VII collagen / protein supplement / gene therapy / epidermal transplantation
Research Abstract

Epidermolysis bullosa consists of a group of genetically determined skin disorders where minor trauma causes blisters and erosions in the skin and mucous membranes. Recent advance in epidermolysis bullosa research has identified several causative genes which encoding structural proteins for stability in adhesion of the epidermis and the dermis. However, there is no effective treatment for epidermolysis bullosa.
The purposes of this study are to make a precise diagnosis of the patients with epidermolysis bullosa and to develop a protein therapy based on novel strategy, in which we produce defective recombinant protein and provide it to skin lesions of the patients.
In this study we performed mutation analysis of many patients in Japan as well as foreign countries. Also, we treated patients with autologous epidermal sheet graft in Hokkaido University. Furthermore, we succeeded in purification of recombinant type VII collagen which majority of severe patients with epidermolysis bullosa lack in Japan.
In this study, our mutation analysis of epidermolysis bullosa resulted in disclosing new findings about epidermolysis bullosa diagnostic and pathophysiological aspects. Although protein therapies using recombinant enzymes are ongoing in clinical practice, those using structural proteins has been never tried before. This study provide a great potential of protein therapy in the future.

  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Arita K, et al.: "Squamous cell carcinoma in a patien with non-bullous congenital ichthyosiform erythroderma."Br J Dermatol. 148. 363-384 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu T, et al.: "Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor (MIF) : Its potential anti-inflammatory action."Clin Exp Allergy. 34. 103-109 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuzaki Y, et al.: "Keratinocyte responsive element 3 : analysis of a keratinocyte-specific regulatory sequence in the 230 kDa bullous pemphigoid antigen promoter."J Invest Dermatol. 120. 308-312 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sawamura D, et al.: "Epidermolysis bullosa : directions for future research and new challenges for treatment."Arch Dermatol Res. 295 Suppl 1. S34-S42 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki H, et al.: "Squamous cell carcinoma developing in a 12-year-old boy with non Hallopeau-Siemens recessive dystrophic epidermolysis bullosa."Br J Dermatol. 148. 1047-1050 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Liu Y, et al.: "Immunofluorescence studies using skin sections of recessive dystrophic epidermolysis bullosa patients indicated that the antigen of anti-p200 pemphigoid is not a fragment of type VII collagen."J Dermatol Sci. 32. 125-129 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] McMillan JR, et al.: "Epidermal basement membrane zone components : ultrastructural distribution and molecular interactions."J Dermatol Sci. 31. 169-177 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] McMillan JR, et al.: "Ultrastructural orientation of laminin 5 in the epidermal basement membrane : an updated model for basement membrane organization."J Histochem Cytochem. 51. 1299-1306 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] McMillan JR, et al.: "Alterations in desmosome size and number coincide with the loss of keratinocyte cohesion in skin with homozygous and heterozygous defects in the desmosomal protein plakophilin 1."J Invest Dermatol. 121. 96-103 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] McMillan JR, et al.: "Immunomapping of EBA sera to multiple epitopes on collagen VII : further evidence that anchoring fibrils originate and terminate in the lamina densa."Exp Dermatol. 12. 261-267 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Siegel DH, et al.: "Loss of kindlin-1, a human homolog of the 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
  • [Publications] Tomita Y, et al.: "Simultaneous occurrence of three squamous cell carcinomas in a recessive dystrophic epidermolysis bullosa patient."Acta Derm Venereol. 83. 225-226 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuji Y, et al.: "Changing pattern of deiminated proteins in developing human epidermis."J Invest Dermatol. 120. 817-822 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuyama N, et al.: "The dinucleotide microsatellite polymorphism of the IFNAR1 gene promoter correlates with responsiveness of hepatitis C patients to interferon."Hepatol Res. 25. 221-225 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Satoh M, et al.: "Innate apoptosis of human B lymphoblasts transformed by Epstein-Barr virus : modulation by cellular immortalization and senescence."Cell Struct Funct. 28. 61-70 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arita K, et al.: "Severely hyperkeratotic erythroderma associated with Hodgkin's disease - Dose high serum G-CSF contribute to the formation of skin lesions?"J Am Acad Dermatol. 49. 772-773 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sasaki H, et al.: "A novel Sp1-family-related cis-acting element for transcription of type VII collagen gene (COL7A1)."J Dermatol Sci. 32. 239-242 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato-Matsumura KC, et al.: "A novel insertion mutation in COL7A1 identified in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa."Acta Dermato-Venereol. 83. 137-138 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arita K, et al.: "Squamous cell carcinoma in a patien with non-bullous congenital ichthyosiform erythroderma."Br J Dermatol. 148. 363-384 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu T, et al.: "Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor (MIF) : Its potential anti-inflammatory action."Clin Exp Allergy. 34. 103-109 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuzaki Y, et al.: "Keratinocyte responsive element 3 : analysis of a keratinocyte-specific regulatory sequence in the 230 kDa bullous pemhigoid antigen promoter"J Invest Dermatol. 120. 308-312 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sawamura D, et al.: "Epidermolysis bullosa : directions for future research and new challenges for treatment."Arch Dermatol Res. 295 Suppl 1. S34-S42 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawasaki H, et al.: "Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa."Br J Dermatol. 148. 1047-1050 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Liu Y, et al.: "Immunofluorescence studies using skin sections of recessive dystrophic epidermolysis bullosa patients indicated that the antigen of anti-p200 pemphigoid is not a fragment of type VII collagen."J Dermatol Sci. 32. 125-129 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] McMillan JR, et al.: "Epidermal basement membrane zone components : ultrastructural distribution and molecular interactions."J Dermatol Sci. 31. 169-177 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] McMillan JR, et al.: "Ultarastructural orientation of laminin 5 in the epidermal basement membrane : an updated model for basement membrane organization."J Histochem Cytochem. 51. 1299-1306 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] McMillan JR, et al.: "Alterations in desmosome size and number coincide with the loss of keratinocyte cohesion in skin with homozygous and heterozygous defects in the desmosomal protein plakophilin 1."J Invest Dermatol. 121. 96-103 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] McMillan JR, et al.: "Immunomapping of EBA sera to multiple epitopes on collagen VII : further evidence that anchoring fibrils originate and terminate in the lamina densa."Exp Dermatol. 12. 261-267

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Siegel DH, et al.: "Loss of kindlin-1, a human homolog of the 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
  • [Publications] Tomita Y, et al.: "Simultaneous occurrence of three squamous cell carcinomas in a recessive dystroplic epidermolysis bullosa patient."Acta Derm Venereol. 83. 2225-226

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuji Y, et al.: "Changing pattern of deiminated proteins in developing human epidermis."J Invest Dermatol. 120. 817-822 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuyama N, et al.: "The dinucleotide microsatelliste polymorphism of the IFNAR1 gene promoter correlates with responsiveness of hepatitis C patients to interferon."Hepatol Res. 25. 221-225

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Satoh M, et al.: "Innate apoptosis of human B lymphoblasts transformed by Epstein-Barr virus : modulation by cellular immortalization and senescence."Cell Struct Funct. 28. 61-70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arita K, et al.: "Severely hyperkeratotic erythroderma associated with Hogkin's diseas-Dose high serum G-CSF contribute to the formation of skin lesions?"J Am Acad Dermatol. 49. 772-773

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sasaki H, et al.: "A novel Spl-family-related cis-acting element for transcription of type VII collagen gene (COL7A1)"J Dermaol Sci. 32. 239-242

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato-Matsumura KC, et al.: "A novel insertion mutation in COL7A1 identified in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa"Acta Dermato-Venereol. 83. 137-138

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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