The role of cardiac specific long non-coding RNA in pathological mechanism of cardiac hypertrophy and heart failure.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670405
• 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): 2014-04-01 – 2016-03-31
• Keywords: ノンコーディングRNA

Outline of Final Research Achievements

The re-upregulation of fetal cardiac genes in heart failure has been reported. Using gene trap approach, among embryonic cardiac specific expressed-clones of long non-coding RNA, cardiac specific long non-coding RNA X (CSLR-X) was identified. The newly established CAG promoter-driven CSLR-X (CAG-CSLR-X) transgenic mice showed no differences of cardiac morphology and cardiac function between CAG-CSLR-X Tg (Tg) and their littermate wild-type mice. To investigate the cardiac function of CAG-CSLR-X, we operated transverse aorta constriction model (TAC) using Tg mice. Ultrasonic echocardiography revealed that Tg mice showed preserved cardiac systolic function, as estimated by fractional shortening analysis, compared with their littermate wild-type mice at 4 weeks after TAC surgery.

Free Research Field

分子遺伝学/循環器病態学

Academic Significance and Societal Importance of the Research Achievements

lncRNA自体がまだ発表されて間もないため、その解析は主に培養細胞系を用いて行われおり、遺伝子改変マウスの個体を用いた解析はほとんど行われていない。さらにlncRNAと心機能および心疾患の分子機構に関する報告は現在、数少なく、今回の研究は非常に貴重な成果である。lncRNA CSLR-Xの新たな作用機構の解明だけでなく、種々の遺伝子改変マウスを用いることで心臓における分子機構が明らかとなり、さらには心不全病態形成における分子機構の基盤研究だけでなく、心不全の予防医学に向けた新規治療法開発へと期待される。