2023 Fiscal Year Final Research Report

Effects of CCN2 on myofibroblast differentiation, which is key player of fibrosis, through transcription factor-like functions

Research Project

PDF

Project/Area Number	20K09889
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57010:Oral biological science-related
Research Institution	Okayama University
Principal Investigator	NISHIDA Takashi 岡山大学, 医歯薬学域, 准教授 (30322233)
Co-Investigator(Kenkyū-buntansha)	滝川正春岡山大学, 医歯薬学域, 教授 (20112063) 久保田聡岡山大学, 医歯薬学域, 教授 (90221936) 服部高子岡山大学, 医歯薬学域, 助教 (00228488) 青山絵理子岡山大学, 医歯薬学域, 助教 (10432650) 高江洲かずみ (河田かずみ) 岡山大学, 医歯薬学域, 助教 (10457228)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	CCN2 / 線維化 / 核内移行 / 筋線維芽細胞 / PU.1
Outline of Final Research Achievements	It has been known that Cellular communication network factor 2 (CCN2) is one of responsible molecule for fibrosis and that it has a signal peptide at the N-terminus and nuclear localization signal-like (NLSL) around C-terminus. However, the involvement of this NLSL in onset and progression of fibrosis remains unclear. This study reveals that CCN2 translocases into the nucleus of fibroblasts and interacts with the promoter of PU.1, which regulates the differentiation to myofibroblasts that are key player for fibrosis. These findings suggest that CCN2 controls the production of PU.1 as a transcription co-factor and contributes to the aggravation of fibrosis.
Free Research Field	口腔生化学
Academic Significance and Societal Importance of the Research Achievements	今回の研究成果は、成長因子としての作用を持つCCN2が核内に移行し、転写共役因子として線維化の発症と進行に影響を与えることを示しており、CCN2のこれまで明らかになっていなかった機能を示した点に学術的な意義がある。また、本研究は線維化の増悪に関与する筋線維芽細胞の分化機構の解明の一助にもなると考えられ、線維化の新たな治療戦略を構築する上でも意義は大きい。線維化はこれまで有効な治療薬がなく、本研究の成果は線維化の新たな治療薬の可能性を示しており、その社会的な意義は大きい。