2018 Fiscal Year Final Research Report

Function and regulation of Nrf2 in mesenchymal stem cells

Research Project

PDF

Project/Area Number	16K01484
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Rehabilitation science/Welfare engineering
Research Institution	Kindai University
Principal Investigator	FUKUDA Kanji 近畿大学, 医学部, 教授 (50201744)
Co-Investigator(Kenkyū-buntansha)	小野寺勇太近畿大学, 医学部附属病院, 助手 (30510911) 寺村岳士近畿大学, 医学部附属病院, 講師 (40460901) 丹羽淳子近畿大学, 医学部, 講師 (60122082) 高橋英夫近畿大学, 医学部, 教授 (60335627) 竹原俊幸近畿大学, 医学部, 助教 (60580561)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	間葉系幹細胞 / 幹細胞老化 / ロコモティブシンドローム / miRNA
Outline of Final Research Achievements	Accumulation of reactive oxygen species (ROS) is a major indication of aging and could be a direct reason for tissue degeneration. Nrf2 is a master transcription factor for the anti-oxidation-related genes and disturbing its expression level lead to attenuation of the redox systems. We found that expression of Nrf2 is suppressed in aged bone marrow tissues and muscles. We found here that aging-associated-inflammation commonly observed in various aged tissues and disruption of Notch1 expression trigger overexpression of miR-155, and miR-155 inhibits expression of Nrf2 through suppression of C/ebpβ. This mechanism is conserved in bone marrow mesenchymal stem cells (MSCs) and muscular satellite cells. Results of transcriptome analysis on Nrf2 KO mice showed that Nrf2 could participate various stem cell function such as self-renewal and maintenance of epigenetic status, thus regulation of Nrf2 could be an attractive target molecule for anti-aging therapy of various locomotive tissues.
Free Research Field	リハビリテーション医学
Academic Significance and Societal Importance of the Research Achievements	本研究成果は、加齢に伴う運動組織の退行メカニズムの解明に寄与する。また、本研究では運動負荷、ヒアルロン酸投与の二法により、抗酸化ストレスあるいは幹細胞機能の維持に重要な転写因子Nrf2の発現を賦活できる可能性を報告している。研究成果をさらに発展させることで、近年社会的な問題になっているロコモティブシンドロームをはじめとした、加齢性運動機能障害の新規治療法の開発に貢献しうると考えられる。