Elucidation of molecular basis of heart failure development from the point of view of epigenome regulation.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15445
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kumamoto University
• Principal Investigator: Oike Yuichi 熊本大学, 大学院生命科学研究部(医), 教授 (90312321)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 心不全 / ノンコーディングRNA

Outline of Final Research Achievements

We investigated molecular mechanisms of cardiac specific long non-coding RNA X (CSLR-X), which was identified among embryonic cardiac specific expressed-clones of long non-coding RNA with gene trap approach, under heart failure development and progression. To assess whether cardiac phenotypes observed in CSLR-X KO (KO) mice were attributable to loss of cardiomyocyte-derived CSLR-X, we have established cardiac specific overexpressed CSLR-X Tg (Tg) mice and cardiac specific CSLR-X conditional KO (CKO) mice. Tg and CKO mice showed no differences of cardiac morphology and cardiac function compared with their littermate wild-type mice, respectively. And to identify mechanisms underlying the effect of CSLR-X on cardiac function, we performed the proteome analysis of whole heart tissues using KO, CAG-CSLR-X Tg and wild-type mice and identified several candidate proteins.

Free Research Field

循環器病態学

Academic Significance and Societal Importance of the Research Achievements

lncRNAは存在が認識され間もないため、機能解析は主に培養細胞を用いて行われており、生体での機能解明の報告は数少ない。さらに、細胞質lncRNAの作用機構は核内lncRNAよりも、作用機構が十分に明らかになっていない。本研究によって得られる成果により、心肥大・心不全の病態形成に関わる世界初の細胞質lncRNAの作用機構が明らかとなり、予後不良の疾患である心不全へのlncRNAという新たな観点からの新規治療法開発の基盤研究としての可能性が期待される。