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Analysis of the expression and roles of receptor-type tyrosine kinase in keloid tissue

Research Project

Project/Area Number 10671682
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionNagasaki University School of Medicine

Principal Investigator

YAMASHITA Shunichi (1999)  Nagasaki University School of Medicine, Professor, 医学部, 教授 (30200679)

村上 隆一 (1998)  長崎大学, 医学部・附属病院, 講師 (70239507)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Ryuichi  Nagasaki University School of Medicine, Lecturer, 医学部, 助手 (70239507)
FUJII Tohru  Nagasaki University School of Medicine, Professor, 医学部, 教授 (60136661)
山下 俊一  長崎大学, 医学部, 教授 (30200679)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsKeloid / Receptor-type tyrosine kinase / IGF-IR / アポトーシス / IGF-I receptor
Research Abstract

Keloid is a dermal fibroproliferative tissue of unknown etiology. Protein tyrosine kinases (PTKs) play an important role in the regulation of cell growth and differentiation. Activation of PTK cascade in keloid fibroblasts is thought to be closely linked to abnormal cell proliferation and migration.
In order to examine the expression of receptor-type PTK in normal and keloid fibroblasts, we used the homology cloning method with a degenerated primer. Although 8 receptor-type PTK genes were expressed in both fibroblasts, insulin-like growth factor-I receptor (IGF-IR) was overexpressed only in keloid fibroblasts. Immunohistochemical analysis confirmed the high expression of IGF-IR.
To examine the functional properties of the IGF-I/IGF-IR pathway, we investigated cell proliferation invasion activity and apoptosis of both types of fibroblasts. The mitogenic effect of IGF-I on both fibroblasts was very weak compared with serum stimulation. In contrast, the invasive activity of keloid fibroblasts was markedly increased in the presence of IGF-I, and inhibited by a neutralizing antibody against IGF-IR. Also keloid fibroblasts resisted apoptosis induced by C2-ceramide. Exogenously added IGF-I enhanced the resistance of keloid fibroblasts to ceramide-induced apoptosis. Wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor suppressed the anti-apoptotic action of IGF-I in keloid fibroblasts.
These findings suggest that the involvement of activated IGF-I/IGF-IR signal in the pathogenesis of keloid by enhancing the invasive activity and the resistance to apoptosis of fibroblasts.

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] M. Fujioka, et al.: "Comparative study of inferior alveolar disturbance restoration after sagittal split osteotomy by means of bicortical versus monocortical osteosynthesis"Plast Reconstr Surg. 102. 37-41 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] R. Murakami, et al.: "Free groin flap for reconstruction of the tongue and oral floor"J Reconstr Microsurg. 14. 49-55 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Mutaf, et al.: "expansion of venous flaps : An experimantal study in rats"Brit J Plast Surg. 53. 393-401 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Yoshimoto, et al.: "Increased proliferative activity of osteoblasts in congenital hemifacial hypertrophy"Plast Reconstr Surg. 102. 1605-1610 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Yamashita: "Editorial: Sporadic multiple endocrine neoplasa type 2A"Intern Med. 38. 80 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Yoshimoto, et al.: "Overexpression of insulin-like growth factor-1 (IGF-1) receptor and the invasiveness of cultured keloid fibroblasts"Am J Pathol. 154. 883-889 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 藤井徹: "標準形成外科科学"医学書院(印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Fujioka, et al.: "Comparative study of inferior alveolar disturbance restoration after sagittal split osteotomy by means of bicortical versus monocortial osteosynthesis"Plast Reconstr Surg. 102. 37-41 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] R.Murakami, et al.: "Free groin flap for reconstruction of the tongue and oral floor"J reconstr Microsurg. 14. 49-55 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Mutaf, et al.: "An experimental study in rats"Brit J Plast Surg. 53. 393-401 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H.Yoshimoto, et al.: "Increased proliferative activity of osteoblasts in congenital hemifacial hypertrophy"Plast Reconstr Surg. 102. 1605-1610 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Yamashita, et al.: "Editorial: Sporadic multiple endocrine neoplasa type 2A"Intern Med. 38:2. 80 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H.Yoshimoto, et al.: "Overexpression of insulin-like growth factor-1(IGF-I) receptor and the invasiveness of cultured keloid fibroblasts"Am J Pathol. 154. 883-889 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] R.M.Abdur,S.Akita,M.S.Rzzaque,et al: "Coadministration of basic fibroblast growth factor and sucrose octasufato (Surface) facilitates the rat dorsal flap survivor and friability"Journal of Plastic and Reconstructive Surgery. 103・3. 941-948 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Yoshimoto,H.Ishihata,A.Ohtsuru,et al: "Overexpression of insulin-like growth factor-I (IGF-I)receptor and the invasiveness of cultured keloid fibroblasts"American Journal of Pathology. 154・3. 883-889 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] R.Murakami,K.Tanaka,K.Kobayashi et al: "Free groin flap for reconstruction of the tongue and oral floor"J Reconstr.Microsurg. 14・1. 49-55 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Nakano,K.Yoshimura,M.Oikawa et al: "Identification characterization and mapping of the human zis (zinc-finger,splicina) gene"Gene. 255. 59-65 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Yoshimoto,H.Yano,K.Kobayashi et al: "Increased proliferative activity of osteoblasts in congenital novifacial hypertrophy"Plast Reconstr Surg. 102・5. 1605-1610 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 藤井徹: "標準形成外科学 第4版"医学書院. 320 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshimoto H,Fujii T,Yamashita S,et al: "Overexpression of Insulin-like Growth Factor-1 (IGF-1) Receptor and the Invasiveness of Cultured Keloid Fibroblasts" The American Journal of Pathology. (in press).

    • Related Report
      1998 Annual Research Report

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

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