Molecular pharmacological analysis of anti-inflammatory effects of PAI-1 inhibitor

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860185
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kyoto University (2014); Tohoku University (2013)
• Principal Investigator: ATSUHIKO Ichimura 京都大学, 健康長寿社会の総合医療開発ユニット, 特定助教 (10609209)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 分子薬理学 / 創薬

Outline of Final Research Achievements

This research was conducted with the aim to elucidate the molecular pharmacological mechanism of anti-inflammatory effect of PAI-1 inhibitors. The suitable pathological model of inflammation to evaluate efficacy of PAI-1 inhibitors was searched. As a result, we have successfully found anti-inflammatory effect of PAI-1 inhibitors on high fat diet (HFD)-induced obesity model. PAI-1 inhibitors attenuated HFD-induced impaired systemic glucose and energy metabolism. Further analyses of molecular mechanisms of the efficacy of PAI-1 inhibitors demonstrated that PAI-1 inhibitors suppressed accumulation of fat in adipocyte accompanying with the inhibition of infiltration of inflammatory macrophages into adipose tissue and the liver. These results suggest the possibility of PAI-1 inhibitors as novel therapeutic agent of metabolic disorders.

Free Research Field

分子薬理学