Molecular mechanism of proliferation of myofibroblasts in diabetic retinopathy
| Project/Area Number |
15590946
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Ehime University |
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Principal Investigator |
NISHIDA Wataru Ehime University, University Hospital, Instructor, 医学部附属病院, 助手 (80271089)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Diabetes / Retinopathy / Myofibroblasts / 筋線維芽細胞 / 糖尿病網膜症 / 平滑筋様細胞 / 形質転換 |
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| 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.
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Report
(3 results)
Research Products
(12 results)
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[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
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Journal Title
Circulation 108
Pages: 2524-2529
Description
「研究成果報告書概要(和文)」より
Related Report
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[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
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Journal Title
Circulation 108
Pages: 2524-2529
Description
「研究成果報告書概要(欧文)」より
Related Report
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