Functional screening for novel molecules related to endothelial dysfunction in the ubiquitin system and the potential of their clinical application.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670365
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Osaka University
• Principal Investigator: Hiromi Rakugi 大阪大学, 医学系研究科, 教授 (20252679)
• Co-Investigator(Renkei-kenkyūsha): KANEDA Yasufumi 大阪大学, 大学院医学系研究科 ゲノム生物学講座 遺伝子治療学分野, 教授 (10177537)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 老化 / 血管内皮 / ユビキチン系 / 遺伝子機能スクリーニング / 加齢性疾患 / Annexin A1

Outline of Final Research Achievements

We found the ubiquitin system-related secretory molecule AnnexinA1 (ANXA1) derived from cDNA library of vascular endothelial cell by the functional gene screening for factors inducing oxidative stress in human dermal fibroblast. Although ANXA1 has been reported to be anti-inflammatory molecule, we speculated ANXA1 was cleaved in the milieu in which cell senescence was induced by oxidative stress and C-terminal fragment of ANXA1 (CT-ANXA1) showed proinflammatory action. CT-ANXA1-induced oxidative stress could evoke cell senescence and enhance secretion of inflammatory molecules in endothelial cells, potentially leading senescence-associated secretory phenomenon (SASP). Currently, we are investigating the pathological contribution of CT-ANXA1 on the various age-related diseases initiated by vascular endothelial dysfunction associated with SASP.

Free Research Field

老年医学