The transcriptional regulation of calcium induced cell death in heart

钙诱导心脏细胞死亡的转录调控

• 批准号: 23659110
• 负责人: NAKAYAMA Hiroyuki
• 金额: $ 2.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659110/
• 关键词: カルシウム; 細胞死; 転写因子; 心不全

Recent studies demonstrated that the osteopontin (OPN), an acid phosphoprotein plays pivotal roles in cardiac hypertrophy and failure. An osteogenic transcription factor Runx2 regulates the expression of OPN in osteoblasts. In the present study, we attempted to examine the pathological role of Runx2 in cardiac hypertrophy and failure. We generated transgenic mice (TG) overexpressing Runx2. Two TG lines (low and high) were obtained and high-expressing TG (HE-TG) showed cardiac hypertrophy and premature death within 8 weeks of age. In addition, HE-TG mice demonstrated decreased fractional shortening assessed by echocardiography. In response to pressure overload, low expressing TG (LE-TG) demonstrated higher mortality and enhanced cardiac hypertrophic response after TAC. In conclusion, targeted expression of Runx2 in heart mediates cardiac dysfunction and hypertrophy in mice. Thus, Runx2 could be a novel therapeutic target for heart failure.

骨桥蛋白（OPN）是一种酸性磷酸化蛋白，近年来研究表明，OPN在心肌肥厚和心力衰竭中起着重要作用。成骨转录因子Runx 2调节成骨细胞中OPN的表达。在本研究中，我们试图研究Runx 2在心脏肥大和衰竭中的病理作用。我们产生过表达Runx 2的转基因小鼠（TG）。获得了两个TG品系（低和高），高表达TG（HE-TG）表现出心脏肥大和8周龄内的过早死亡。此外，HE-TG小鼠表现出通过超声心动图评估的缩短分数降低。低表达TG（LE-TG）组在压力负荷时死亡率高，心脏肥大反应增强。总之，Runx 2在心脏中的靶向表达介导了小鼠的心功能不全和肥大。因此，Runx 2可能是心力衰竭的新治疗靶点。

项目成果

心筋特異的Runx2 過剰発現マウスは心肥大を惹起する

小鼠过度表达心肌特异性 Runx2 诱导心脏肥大

• 发表时间: 2012
• 作者: 濱谷辰斗;中山博之;松浪佐知;松尾玲男;藤尾慈
• 通讯作者: 藤尾慈

Cardiac-specific overexpression of Runx2 mediates cardiac hypertrophy and dysfunction in mice

Runx2 心脏特异性过度表达介导小鼠心脏肥大和功能障碍

• 发表时间: 2012
• 作者: Hara-Yokoyama M.;Kukimoto-Niino M.;Terasawa K.;Harumiya S.;Podyma-Inoue K. A.;Hino N.;Sakamoto K.;Itoh S.;Hashii N.;Hiruta Y.;Kawasaki N.;Mishima-Tsumagari C.;Kaitsu Y.;Matsumoto T.;Wakiyama M.;Shirouzu M.;Kasama T.;Ta;中山 博之
• 通讯作者: 中山 博之

心筋Runx2過剰発現マウスは心肥大を惹起する

心肌 Runx2 过度表达的小鼠诱导心脏肥大

• 发表时间: 2012
• 作者: Murase K;Mori K;Yoshimura C;Aihara K;Chihara Y;Azuma M;Harada Y;Toyama Y;Tanizawa K;Handa T;Hitomi T;Oga T;Mishima M;Chin K;濱谷辰斗
• 通讯作者: 濱谷辰斗