| Project/Area Number |
14570994
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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 |
Hematology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
SUGO Teruko Jichi Medical School, Cell and molecular medicine, Instructor, 医学部, 講師 (60183844)
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| Co-Investigator(Kenkyū-buntansha) |
MADOIWA Seiji Jichi Medical School, Cell and molecular medicine, Instructor, 医学部, 講師 (70296119)
ENDO Hitoshi Jichi Medical School, Biochemistry, Associate Prof., 医学部, 助教授 (50221817)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | fibrinogen / fibrin networks / blood vessels / injury / HUVEC / collagen / wound healing / repairement / プラスミン / 創傷治癒 / 血管壁 / 人工血管 |
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| Research Abstract |
Fibrin formation at the site of injury protects injured site from the environment of blood stream as well as from outflow of blood. We have hypothesized one more function of fibrin clots as a reservoir of the growth factors, cytokines and others by concentrating the many types of inflammatory cells at the site of injury and thus promoting the repair process of the blood vessels. We are expecting the destruction of the fibrin network is connected to the regulation of the repairment. To confirm our hypothesis, we needed to construct the vessel model that can survive long enough to span the wound healing. After many trials and errors, we have found one condition that human umbilical vein endothelial cells (HUVEC) can survive more than two months after reaching confluence. Electron microscopic analysis showed that the mixed collagen (type I and IV) and the heparin sulfate formed uniform 3-D networks of collagen fibers that contains many small pores that can be penetrated by the microvilli
… More
of the HUVEC. Indeed, on the surface of collagen gels, HUVEC penetrate its microvilli into the gels and thus tight attachment had been achieved. Furthermore, many components of extra cellular matrix retained on the surface of collagen gels by the cross-linking just beneath the 1-TUVEC. On this cultivation, HUVEC restored highly resistance toward enzymatic treatment as those had been in the umbilical vein. By using this model system, we are now investigating the role of fibrin structure on the repair from the mechanical wound.
We have also examined the structure of the fibrin networks formed from the purified 30 kinds of dysfibrinogens. By scanning electron microscopic analysis, all the dysfibrinogens purified from the patients reported to have hemorrhage or thrombosis episodes form the different fibrin networks from that of normal. However, we could not detect apparent relationship with the fibrin structure and the clinical symptoms, instead, we observed unique fibrin structure in all the dysfibrinogen with g-Arg-275 to Cys mutation. In these studies, we concluded that the abnormal fibrin structure composed of mesh-like structure with very thin and highly branched fibers seems to be important to the properties of the fiber strength but the plasmin-resistance is the most important factors leading to the delay of the wound healing in the patient (manuscript in preparation). These data coincided on our hypothesis mentioned above. Less
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