下调和上调
血小板源性生长因子受体
生物
蛋白激酶B
条件基因敲除
细胞生物学
PI3K/AKT/mTOR通路
再生(生物学)
细胞生长
癌症研究
生长因子
信号转导
受体
表型
基因
遗传学
作者
Yue Zhang,Jiuling Chen,Lan Hong,Jianqiu Pei,Yandong Li,Xianda Chen,Shen Song,Jiahong Xia,Bin Zhou,Jie Feng,Xinyue Zhang,Shengshou Hu,Yu Nie
出处
期刊:Cell Reports
[Elsevier]
日期:2019-07-01
卷期号:28 (4): 966-978.e4
被引量:44
标识
DOI:10.1016/j.celrep.2019.06.065
摘要
Summary
Platelet-derived growth factor receptor (PDGFR) signaling is involved in proliferation and survival in a wide array of cell types. The role of PDGFR signaling in heart regeneration is still unknown. We find that PDGFR-β signaling decreases in myocardium with age and that conditional activation PDGFR-β in cardiomyocytes promotes heart regeneration. Employing RNA sequencing, we show that the enhancer of zeste homolog 2 (Ezh2) can be upregulated by PDGFR-β signaling in primary cardiomyocytes. Conditional knockout of Ezh2 blocks cardiomyocyte proliferation and H3K27me3 modification during neonatal heart regeneration with Ink4a/Arf upregulation, even in mice with myocyte-specific conditional activation of PDGFR-β. We also show that PDGFR-β controls EZH2 expression via the phosphatidylinositol 3-kinase (PI3K)/p-Akt pathway in cardiomyocytes. Gene therapy with adeno-associated virus serotype 9 (AAV9) encoding activated PDGFR-β enhances adult heart regeneration and systolic function. Our data demonstrate that the PDGFR-β/EZH2 pathway is critical for promoting cardiomyocyte proliferation and heart regeneration, providing a potential target for cardiac repair.
科研通智能强力驱动
Strongly Powered by AbleSci AI