The mechanisms for the progression of hepatic fibrosis through AGE-RAGE system and renin-angiotensin system

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kochi University
• Principal Investigator: HIROSE Akira 高知大学, 教育研究部医療学系臨床医学部門, 助教 (30457395)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ＮＡＳＨ / レニン-アンギオテンシン系 / 終末糖化産物(AGE) / RAGE / 肝線維化

Outline of Final Research Achievements

The signal transduction from advanced glycation end-products (AGE) and the receptor for AGE (RAGE) involved the production of reactive oxygen species (ROS) which were important for the pathogenesis of NASH. Therefore, we investigated the control mechanisms of the hepatic fibrosis through RAS and RAGE-AGE system. It was clarified that the regulation of the expression of RAGE by RAS was depended on the regulation of phosphorylation of PKC-δand PKC-β.The expression of RAGE in liver were regulated by the expression of TNF-αand ROS in NASH. Furthermore, hepatic inflammation and fibrosis were remarkably attenuated without decreased hepatic steatosis in NASH of RAGE knockout mice. Taken together, AGE-RAGE system are important for the development of hepatic fibrosis in the pathogenesis of NASH.

Free Research Field

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