| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Heme oxygenase (HO) is a rate-limiting enzyme in heme degradation pathway. HO-1 is an inducible isoform of HO, and also known as heat shock protein 32, one of the major stress proteins. I reported that HO-1 induction in the various type of tissue injury played an important protective role against oxidative stress. During the liver regeneration, the significant induction of HO-1 was observed in the liver within a day after partial hepatectomy (PH). In the regeneration liver, newly formed blood vessels are fundamental for hepatocyte proliferation. Although increasing intrahepatic angiogenesis after PH has been reported, little is known about the contribution of vasculogenesis on liver regeneration. In fact, increased blood vessel formation around portal vein was observed in the murine regeneration liver by histological study. Since HO activity has been reported to regulate neovascularization, I investigated the effect of HO-1 induction on neovasculogenesis, using mouse embryonic stem (ES) cells, and human umbilical vein endothelial cells (HUVEC), evaluating not only the cell proliferation by also the blood vessel-like structure formation by CD31-positive cells. HO-1 induction caused by hemin addition to the medium, significantly increased cell proliferation both in ES cells and HUVEC. In ES cells, it also stimulated the blood vessel-like structure formation by CD31-positive cells, which located along the cells expressing HO-1. Although vascular endothelial growth factor (VEGF) stimulated both proliferation and structure formation in HUVEC, hemin treatment resulted in significant proliferation, but inhibition of structure formation.
These results suggested that HO-1 induction observed in the early stage of the regeneration liver, played the different role on neovascularization from VEGF in the course of liver regeneration.
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