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2004 Fiscal Year Final Research Report Summary

Molecular mechanism of proliferation of myofibroblasts in diabetic retinopathy

Research Project

Project/Area Number 15590946
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionEhime University

Principal Investigator

NISHIDA Wataru  Ehime University, University Hospital, Instructor, 医学部附属病院, 助手 (80271089)

Co-Investigator(Kenkyū-buntansha) HASHIRAMOTO Mitsuru  Ehime University, University Hospital, Instructor, 医学部附属病院, 助手 (40346680)
MAKINO Hideichi  Ehime University, School of Medicine, Professor, 医学部, 教授 (50009578)
OSAWA Haruhiko  Ehime University, School of Medicine, Associcate Professor, 医学部, 助教授 (90294800)
OHNUMA Hiroshi  Ehime University, School of Medicine, Instructor, 医学部, 助手 (00294794)
Project Period (FY) 2003 – 2004
KeywordsDiabetes / Retinopathy / Myofibroblasts
Research Abstract

Diabetic retinopathy is one of the most important vascular complications in diabetes. It is well known that angiogenesis plays pivotal roles in the development of diabetic retinopathy, but the precise mechanism is still unclear. We have been studied the involvement of dedifferentiation of smooth muscle cells (Sacs) in atherosclerosis and found that the proliferation of Sacs are triggered by simultaneous stimulation of ERK and p38MAPK cascades. We also noted that there are common pathogenesis in atherosclerosis, lung fibrosis, liver fibrosis, and nephritis. Under these circumstances, smooth muscle-like cells, such as Ito cells, lung myofibroblasts, mesangium cells, remarkably proliferate in the lesions. We named this pathogenesis as "Myofibroblastosis" and hypothesized that diabetic retinopathy is also included in this new entity.
Using primary culture system of differentiated Sacs, we found that unsaturated lysophosphatidic acid (LPA) is one of the most potent inducer of phenotypic dedifferentiation, and administration of LPA induced progression of intimal thickening in rat carotid artery balloon-injury model (Circulation 108:1746,2003). We also identified new inducer of phenotypic dedifferentiation in the conditioned medium. This factor is a member of EGF family, Epiregulin (Circulation 108:2524,2003). Epiregulin activated both of ERK and p38-MAPK cascades and promptly exchanged the differentiated phenotype of Sacs into dedifferentiated state. Finally, we identified over-expression of EGF family and proliferation of smooth muscle-like cells in the tissue excised from the patients of diabetic retinopathy. We concluded that there is a common pathogenesis in diabetic retinopathy and atherosclerosis.

  • Research Products

    (8 results)

All 2005 2004 2003

All Journal Article (8 results)

  • [Journal Article] 発症時コクサッキーB3ウィルス中和抗体価の上昇がみられた劇症1型糖尿病の1例2005

    • Author(s)
      西田亙, 長谷部晋士, 川村良一, 柱本満, 大沼裕, 大澤春彦, 牧野英一
    • Journal Title

      糖尿病 (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A case of fulminant type 1 diabetes associated with high titer of Coxsackie B3 virus antibody2005

    • Author(s)
      Nishida W, Hasebe S, Kawamura R, Hashiramoto M, Onuma H, Osawa H, Makino H
    • Journal Title

      Journal of the Japan Diabetes Society (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 糖尿病合併症増加の因子(1960年代網膜症はまれであった)2004

    • Author(s)
      西田 亙, 牧野 英一
    • Journal Title

      綜合臨床 53(4)

      Pages: 1473-1475

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The factors which increase diabetic comlications2004

    • Author(s)
      Nishida W, Makino H
    • Journal Title

      Sougou-rinshou 53 (4)

      Pages: 1473-1475

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Vascular Remodeling Induced by Naturally Occuring Unsaturated Lysophosphatidic Acid In Vivo2003

    • Author(s)
      Yoshida K, Nishida W, Hayashi K, Ohkawa Y, Ogawa A, Aoki J, Arai H, Sobue K
    • Journal Title

      Circulation 108

      Pages: 1746-1752

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Epiregulin as a Major Autocrine/Paracrine Factor Released From ERK-and p38MAPK-Activated Vascular Smooth Muscle Cells2003

    • Author(s)
      Takahashi M, Hayashi K, Yoshida Km, Ohkawa Y, Komurasaki T, Kitabatake A, Ogawa A, Nishida W, Yano M, Monden M, Sobue K
    • Journal Title

      Circulation 108

      Pages: 2524-2529

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Vascular remodeling induced by naturally occurring unsaturated lysophosphatidic acid in vivo.2003

    • Author(s)
      Yoshida K, Nishida W, Hayashi K, Ohkawa Y, Ogawa A, Aoki J, Arai H, Sobue K
    • Journal Title

      Circulation 108

      Pages: 1746-1752

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells.2003

    • Author(s)
      Takahashi M, Hayashi K, Yoshida K, Ohkawa Y, Komurasaki T, Kitabatake A, Ogawa A, Nishida W, Yano M, Monden M, Sobue K
    • Journal Title

      Circulation 108

      Pages: 2524-2529

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

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Published: 2006-07-11  

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