Posttranslational modification-dependent FoxO1 target genes in endothelial cells and its medical application

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15354
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ogawa Yoshihiro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70291424)
• Research Collaborator: TSUCHIYA Kyoichiro ; SHIBA Kumiko
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: インスリン抵抗性 / リポカリン2

Outline of Final Research Achievements

Insulin resistance and hyperglycemia activate transcription factor FoxO1 by dephosphorylation and deacetylation, respectively. We aimed to elucidate the pathophysiological roles of FoxO1 in diabetes-associated vascular injury, by identifying target genes of FoxO1 in endothelial cells and examining the regulatory mechanisms by FoxO1. Constitutive active FoxO1 mutant significantly induced Lcn2 (lipocalin-2/NGAL) gene in endothelial cells via Akt/NF-κB-dependent manner. It suggests that FoxO1 promotes type 2 diabetes-associated vascular dysfunction by induction of Lcn2 (lipocalin-2/NGAL) in endothelial cells.

Free Research Field

内分泌代謝学、糖尿病学