Crosstalk of renin-angiotensin system in the chronic liver diseases and therapeutic applications
| 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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Report
(4 results)
Research Products
(61 results)
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[Journal Article] Combination Treatment of Angiotensin-II Type I Receptor Blocker and New Oral Iron Chelator Attenuates Progression of Non-alcoholic Steatohepatitis in Rats.2011
Author(s)
Kaji K, Yoshiji H, Kitade M, Ikenaka Y, Noguchi R, Shirai Y, Aihara Y, Namisaki T, Yoshii J, Yanase K, Tsujimoto T, Kawaratani H, Fukui H.
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Journal Title
Am J Physiol Gastrointest Liver Physiol.
Related Report
Peer Reviewed
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[Journal Article] J Angiogenes Res.2010
Author(s)
Namisaki T, Yoshiji H, Noguchi R, Ikenaka Y, Kitade M, Kaji K, Shirai Y, Aihara Y, Yoshii J, Yanase K, Tsujimoto T, Kawaratani H, Fukui H.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Selective aldosterone blocker ameliorates the progression of non-alcoholic steatohepatitis in rats.2010
Author(s)
Noguchi R, Yoshiji H, Ikenaka Y, Kaji K, Shirai Y, Aihara Y, Yamazaki M, Namisaki T, Kitade M, Yoshii J, Yanase K, Kawaratani H, Tsujimoto T, Fukui H.
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Journal Title
Int J Mol Med. 26(3)
Pages: 407-413
NAID
Related Report
Peer Reviewed
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[Journal Article] Selective aldosterone blocker, eplerenone, attenuates hepatocellular carcinoma growth and angiogenesis in mice.2010
Author(s)
Kaji K, Yoshiji H, Kitade M, Ikenaka Y, Noguchi R, Shirai Y, Yoshii J, Yanase K, Namisaki T, Yamazaki M, Tsujimoto T, Kawaratani H, Fukui H.
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Journal Title
Hepatol Res. 40(5)
Pages: 540-549
NAID
Related Report
Peer Reviewed
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[Journal Article] Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis.2009
Author(s)
Kitade M, Yoshiji H, Noguchi R, Ikenaka Y, Kaji K, Shirai Y, Yamazaki M, Uemura M, Yamao J, Fujimoto M, Mitoro A, Toyohara M, Sawai M, Yoshida M, Morioka C, Tsujimoto T, Kawaratani H, Fukui H.
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Journal Title
World J Gastroenterol. 15(41)
Pages: 5193-5199
Related Report
Peer Reviewed
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[Journal Article] Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic activities.2009
Author(s)
Noguchi R, Yoshiji H, Ikenaka Y, Namisaki T, Kitade M, Kaji K, Yoshii J, Yanase K, Yamazaki M, Tsujimoto T, Kawaratani H, Fukui H.
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Journal Title
Oncol Rep. 22(2)
Pages: 355-360
NAID
Related Report
Peer Reviewed
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[Journal Article] Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma.2009
Author(s)
Yoshiji H, Noguchi R, Toyohara M, Ikenaka Y, Kitade M, Kaji K, Yamazaki M, Yamao J, Mitoro A, Sawai M, Yoshida M, Fujimoto M, Tsujimoto T, Kawaratani H, Uemura M, Fukui H.
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Journal Title
J Hepatol. 51(2)
Pages: 315-321
Related Report
Peer Reviewed
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[Journal Article] Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat.2009
Author(s)
Yoshiji H, Noguchi R, Ikenaka Y, Namisaki T, Kitade M, Kaji K, Shirai Y, Yoshii J, Yanase K, Yamazaki M, Tsujimoto T, Kawaratani H, Akahane T, Aihara Y, Fukui H.
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Journal Title
BMC Res Notes. 2
Pages: 70-70
Related Report
Peer Reviewed
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[Journal Article] Branched-chain amino acids suppress insulin-resistance-based hepatocarcinogenesis in obese diabetic rats.2009
Author(s)
Yoshiji H, Noguchi R, Kitade M, Kaji K, Ikenaka Y, Namisaki T, Yoshii J, Yanase K, Yamazaki M, Tsujimoto T, Akahane T, Kawaratani H, Uemura M, Fukui H.
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Journal Title
J Gastroenterol. 44(5)
Pages: 483-491
NAID
Related Report
Peer Reviewed
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[Journal Article] Impact of insulin resistance on the progression of chronic liver diseases.2008
Author(s)
Kaji K, Yoshiji H, Kitade M, Ikenaka Y, Noguchi R, Yoshii J, Yanase K, Namisaki T, Yamazaki M, Moriya K, Tsujimoto T, Kawaratani H, Akahane T, Uemura M, Fukui H.
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Journal Title
Int J Mol Med. (6)
Pages: 801-808
Related Report
Peer Reviewed
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