Details

Autor(en) / Beteiligte

• Cai, Benzhi
• Ma, Wenya
• Ding, Fengzhi
• Zhang, Lai
• Huang, Qi
• Wang, Xiuxiu
• Hua, Bingjie
• Xu, Juan
• Li, Jiamin
• Bi, Chongwei
• Guo, Shuyuan
• Yang, Fan
• Han, Zhenbo
• Li, Yuan
• Yan, Gege
• Yu, Ying
• Bao, Zhengyi
• Yu, Meixi
• Li, Faqian
• Tian, Ye
• Pan, Zhenwei
• Yang, Baofeng

Titel

The Long Noncoding RNA CAREL Controls Cardiac Regeneration

Ist Teil von

• Journal of the American College of Cardiology, 2018-07, Vol.72 (5), p.534-550

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Adult mammalian heart loses regeneration ability following ischemic injury due to the loss of cardiomyocyte mitosis. However, the molecular mechanisms underlying the post-mitotic nature of cardiomyocytes remain largely unknown. The purpose of this study was to define the essential role of long noncoding ribonucleic acids (lncRNAs) in heart regeneration during postnatal and adult injury. Myh6-driving cardiomyocyte-specific lncRNA-CAREL transgenic mice and adenovirus-mediated in vivo silencing of endogenous CAREL were used in this study. The effect of CAREL on cardiomyocyte replication and heart regeneration after apical resection or myocardial infarction was assessed by detecting mitosis and cytokinesis. An lncRNA CAREL was found significantly up-regulated in cardiomyocytes from neonatal mice (P7) in parallel with loss of regenerative capacity. Cardiac-specific overexpression of CAREL in mice reduced cardiomyocyte division and proliferation and blunted neonatal heart regeneration after injury. Conversely, silencing of CAREL in vivo markedly promoted cardiac regeneration and improved heart functions after myocardial infarction in neonatal and adult mice. CAREL acted as a competing endogenous ribonucleic acid for miR-296 to derepress the expression of Trp53inp1 and Itm2a, the target genes of miR-296. Consistently, overexpression of miR-296 significantly increased cardiomyocyte replication and cardiac regeneration after injury. Decline of cardiac regenerative ability in CAREL transgenic mice was also rescued by miR-296. A short fragment containing the conserved sequence of CAREL reduced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes as the full-length CAREL. LncRNA CAREL regulates cardiomyocyte proliferation and heart regeneration in postnatal and adult heart after injury by acting as a competing endogenous ribonucleic acid on miR-296 that targets Trp53inp1 and Itm2a. [Display omitted]