Development of hepatic anti-fibrotic therapy targeted to angiotensin II receptor antagonist-soppression of collagen production in the Ito cell via TGF-β

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13557045
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Gastroenterology
• Research Institution: Yamagata University
• Principal Investigator: KAWATA Sumio Yamagata Univ. Medical Sch., Professor, 医学部, 教授 (90183285)
• 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)
• Project Period (FY): 2001 – 2002
• Keywords: Hepatic fibrosis / hepatic cirrhosis / chronic hepatitis C / Angiotensin II receptor / angiotensin II / 受容体阻害薬

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.