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2007 Fiscal Year Final Research Report Summary

Mechanism of skin fibrosis by lipid mediators and its clinical trials

Research Project

Project/Area Number 18591234
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionGunma University

Principal Investigator

ISHIKAWA Osamu  Gunma University, graduate school of medicine, Dermatology, Professor (90168188)

Co-Investigator(Kenkyū-buntansha) ABE Masatoshi  Gunma University, graduate school of medicine, Dermatology, Assistant Professor (80302462)
YAMANAKA Masayoshi  Gunma University, graduate school of medicine, Dermatology, Assistant Professor (30323364)
Project Period (FY) 2006 – 2007
Keywordsfibrosis / signal trunsduction / extracellular matrix / collagen / lipid mediators / TGF-beta / phospholipase / MAP kinase
Research Abstract

N-methylethanolamine (MEA), an analog of ethanolamine, has been reported to attenuate cardiac fibrosis and decrease collagen content in rats; however, the mechanism is poorly understood. We therefore aimed to determine the antifibrotic effect of MEA by focusing on extracellular matrix production in human dermal fibroblasts. MEA reduced the expression of type I collagen at the protein, mRNA, and transcriptional levels. In contrast, MEA enhanced the expression of matrix metalloproteinase-1 (MMP-1) at the protein and mRNA levels. MEA did not inhibit the actions of TGF-p, such as type I collagen production, connective tissue growth factor (CTGF) induction, or MMP-1 suppression. These results indicate that the antifibrotic effect of MEA is independent of TGF-β signaling. MEA activated extracellular signal-regulated kinase-1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways, but suppressed the p38 mitogenactivated protein kinase (p38MAPK) pathway. An ERK1/2 inhibitor diminished the inhibitory effect of MEA on type I collagen gene expression, while both a JNK inhibitor and a p38MAPK inhibitor failed to negate MEA actions. These results suggest that MEA inhibits type I collagen gene expression through ERK1/2 signaling. However, ERK 1/2 and JNK inhibitors blocked the MEA-mediated induction of MMP-1, while p38MAPK inhibitor enhanced MMP-1 gene expression induced by MEA. These results indicate that MEA enhanced MMP-1 gene expression through ERK1/2 and JNK signaling and suppressed it through p38 MAPK signaling. Thus, MEA exerts antifibrotic actions through several pathways and is a promising candidate for the treatment of diseases characterized by excessive ECM deposition, such as scleroderma and keloid.

  • Research Products

    (6 results)

All 2007

All Journal Article (2 results) Presentation (4 results)

  • [Journal Article] ヒト線維芽細胞におけるMEA (N-metylethanolamine)の細胞外基質関連遺伝子制御機構2007

    • Author(s)
      山中正義、石川 治
    • Journal Title

      瘢痕・ケロイド治療ジャーナル 1

      Pages: 45-49

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Extracelluler matrix gene expression altered by N-methylethanolamine in Human dermal fibroblasts2007

    • Author(s)
      Masayoshi Yamanaka, Osamu Ishikawa
    • Journal Title

      scar-keloid journal 1

      Pages: 45-49

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Antifibrotic actions of N-methylethanolamine (MEA) in human dermal fibroblasts2007

    • Author(s)
      Masayoshi Yamanaka, Osamu Ishikawa
    • Organizer
      Professor E. Carwile LeRoy Memorial International Workshop on Scleroderma 2007
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20070518-20
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Antifibrotic actions of N-methylethanolamine (MEA) in human dermal fibroblasts.2007

    • Author(s)
      Yamanaka M, Ishikawa O
    • Organizer
      Professor E. Carwile LeRoy Memorial International Workshop on Scleroderma
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20070518-0520
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Antifibrotic actions of N-methylethanolamine (MEA) in human dermal fibroblasts2007

    • Author(s)
      MasayoshiYamanaka, Osamu Ishikawa
    • Organizer
      The 39th Japanese Society for Connective Tissue Research & The 54Th Annual Meeting ofthe Japan Matrix Club
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20070509-11
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ヒト皮膚線維芽細胞におけるMEA (N-methylethanolamine)の抗線維化作用について2007

    • Author(s)
      山中正義、石川 治
    • Organizer
      第39回日本結合組織学会学術大会・第54回マトリックス研究会大会合同学術集会
    • Place of Presentation
      東京
    • Year and Date
      20070509-0511
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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