Development of hepatic anti-fibrotic therapy targeted to angiotensin II receptor antagonist-soppression of collagen production in the Ito cell via TGF-β
| Project/Area Number |
13557045
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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 | 展開研究 |
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| Research Field |
Gastroenterology
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| Research Institution | Yamagata University |
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Principal Investigator |
KAWATA Sumio Yamagata Univ. Medical Sch., Professor, 医学部, 教授 (90183285)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Koji Yamagata Univ. Medical Sch., Assistant Prof., 医学部, 講師 (90250919)
SAITO Takafumi Yamagata Univ. Medical Sch., Assistant Prof., 医学部, 講師 (80250918)
TOGASHI Hitoshi Yamagata Univ. Medical Sch., Associate Prof., 医学部, 助教授 (60192209)
WATANABE Hisayoshi Yamagata Univ. Medical Sch., Assistant, 医学部, 助手 (00332536)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Hepatic fibrosis / hepatic cirrhosis / chronic hepatitis C / Angiotensin II receptor / angiotensin II / 受容体阻害薬 / アンギオテンシンII / アンギオテンシンII受容体 / アンギオテンシン / アンギオテンシン受容体 |
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| Research Abstract |
Anti-fibrotic therapy is expcted to prevent hepatic cirrhosis.
In 2001, we carried out a randomized controlled study on anti-fibrotic therapy for chronic hepatitis C without effect of interferon therapy. 30 consecutive patients with chronic hepatitis C were randomizedly divided into two groups. 15 patients were treated with losartan (50 mg/day), angiotensin II type 1 receptor antagonist, for 3 months. The other 15 patients were followed as controls. After the oral administration, plasma TGF-β1 concentrations, a marker of fibrosis, significantly decreased in the group of losartan whereas the concentrations did not change in the control group. Fibrosis area (%) in the losartan group was reduced with mild significance. This result suggested that blocking of angiotensin II signal leaded to suppression of heparic fibrosis.
In 2002, angiotensin II type 1 receptor antagonist (CS-866) was administered to rat cirrhosis model. The treated rats showed significant decrease in hepatic TGF-β1 and hydroxyproline contents. Histological examination revealed that degree of hepatic fibrosis was much lower in the treated than the controls.
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Report
(3 results)
Research Products
(12 results)
