| Project/Area Number |
20590792
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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 |
Gastroenterology
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| Research Institution | Nara Medical University |
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Principal Investigator |
YOSHIJI Hitoshi Nara Medical University, 医学部, 講師 (40336855)
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| Co-Investigator(Kenkyū-buntansha) |
NOGUCHI Ryuuichi 奈良県立医科大学, 医学部, 特任助教 (30423908)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肝臓学 / 血管新生 / VEGF / 肝発癌 / アンジオテンシン / インスリン抵抗性 / レニンアンジオテンシン系 / 肝線維化 |
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| Research Abstract |
During the period of this grant, we revealed many new findings about the crosstalk of renin-angiotensin system (RAS) in the chronic liver diseases, especially the liver fibrosis development, hepatocarcinogenesis, and the growth of hepatocellular carcinoma (HCC). We reported that angiotensin-II (AT-II) and aldosterone (Ald) play important roles in the respective processes. Both AT-II and Ald could stimulate the proliferation of the activated hepatic stellate cells (HSC) and EC. AT-II and Ald utilizes the PKC and ERK1/2 signaling cascade for the proliferation of endothelial cells (EC), respectively. In the rat hepatocarinogensis studies, we observed that the clinically used safe agents such as vitamin K (VK) and branched-chain amino acid (BCAA) exerted a marked inhibitory effects on the progression of chronic liver diseases. And the combination treatment with these agents and ACE inhibitor (ACE-I)/AT-II receptor blocker (ARB) showed more potent inhibitory effects as compared with any single treatment along with anti-angiogenesis. Furthermore, not only in the animal studies, but also we revealed clinical usefulness with these agents. Collectively, our studies with this grant could contribute to the improvement of prognosis in patients with chronic liver diseases.
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