| Project/Area Number |
11470137
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Saitama Medical School |
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Principal Investigator |
FUJIWARA Kenji Saitama Medical School, Faculty of Medicine, Professor, 医学部, 教授 (80101088)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUI Atsushi Saitama Medical School, Faculty of Medicine,Assistant, 医学部, 助手 (40260484)
NAGOSHI Sumiko Saitama Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50306271)
MOCHIDA Satoshi Saitama Medical School, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20219968)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | Liver transplantation / Microcirculatory disturbance / Sinusoidal endothelial cell / Kupffer cell / Stellate cell / VEGF / Osteopontin / Transgenic mouse / 肝類洞内皮細胞 / 肝星細胞 / angiopoiein / Tie受容体 / osteopontin / 肝再生 / Angiopoietin / TIE受容体 / 肝移植後肝不全 / pericyte / 微小循環 / ヘパリン / プロテオグリカン |
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| Research Abstract |
Sinusoidal endothelial cell (SEC) injury is a major abnormality in the liver transplanted from non-heart beating donors. It is important to protect SECs for the establishment of non-heartbcating liver transplantation
VEGF is a factor essential for maintenance as well as proliferation of SECs in primary culture. We demonstrated that VEGF also acted as avascular permeability factor through up-regulation of the porosity on SECs. Furthermore, VEGF inhibited contraction of stellate cells, pericytes of SECs, suggesting that VEGF can regulate microcirculation in the hepatic sinusoids. VEGF expression in hepatocytes was increased in rat liver after cold preservation in UW solution, but mRNA expressions of VBGFR-1 and VEGFR-1 were decreased prior to the development of SEC in jury These results may suggest that VEGF cannot work effectively on SECs in the cold preserved liver, and also that exogenous VBGF cannot prevent SEC from injury
Kupffer cells were markedly activated in the cold preserved liver, and this activation contributed to SEC injury after orthotopic transplantation of such livers. We found that activated Kupffer cells expressed osteopontin an essential cytokine for initiation of Th1 immune response. Also, we demonstrated that osteopontin played a major role as a chemokine in macrophage migration into the liver using mice with different alleles of osteopontin gene, suggesting that the modulation of osteopontin expression in Kupffer cells may be another strategy for protection of the SECs. We made transgenic mice expressing osteopontin very highly in the liver using human serum amyloid P component promotor as a vector specific for hepatocytes Investigations to prove our hypothesis are now in progress
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