Role of mast cell serine protease (chymase) on acute liver failure

• Project/Area Number: 26461932
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka Medical College
• Principal Investigator: HIROKAWA Fumitoshi 大阪医科大学, 医学部, 講師 (20322373)
• Co-Investigator(Kenkyū-buntansha): 内山 和久 大阪医科大学, 医学部, 教授 (80232867) ; 高井 真司 大阪医科大学, 医学研究科, 教授 (80288703)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 急性肝不全 / キマーゼ / ＭＭＰ / 阻害薬 / 肥満細胞 / マウス / セリンプロテアーゼ / 炎症細胞 / RT-PCR / 免疫染色

Outline of Final Research Achievements

The role of mast cell serine protease (chymase) was investigated in a mouse acute liver failure model. Hepatic chymase activity was significantly increased just after lipopolysaccharide/D-galactosamine (LPS+Galn) injection. Seven hours after LPS+Galn injection, MMP-9, TNF-and MPO were increased, but they were significantly suppressed by treatment with chymase inhibitor 1 hour after LPS+Galn injection, resulting in the increase of survival rate after LPS+Galn injection. Chymase plays an important role in the development of acute liver failure, and chymase inhibitor prevente the acute liver failure.