Notch1 signaling stimulates proliferation of immature cardiomyocytes.
Notch1 signaling stimulates proliferation of immature cardiomyocytes.
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Notch1 信号传导刺激未成熟心肌细胞的增殖。
DOI：
10.1083/jcb.200806091
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发表时间：
2008-10-06
期刊：
影响因子：
--
通讯作者：
Giacca M
中科院分区：
文献类型：
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作者：
Collesi C;Zentilin L;Sinagra G;Giacca M
在胚胎、胎儿和早期新生儿生命中控制心肌细胞增殖的分子机制的识别对于利用这些信息促进心脏再生似乎是最有意义的。在这里，我们展示了新生大鼠心肌细胞的增殖能力被Notch通路的持续激活所强烈地刺激。我们发现Notch1在体外和体内增殖的心肌细胞中都有表达，并且心脏中Notch1阳性细胞的数量随着年龄的增长而减少。NOTCH1在ICM中的表达与其Jagged1配体在非心肌细胞支持细胞上的表达平行。抑制ICM中的Notch信号可阻断其增殖并诱导其凋亡；相反，Jagged1或其激活形式使用腺相关病毒的结构性表达激活Notch信号可显著刺激ICM的增殖信号并促进ICM的扩张。心肌细胞中Notch信号的维持或重新激活可能是创新再生治疗的一个有趣的靶点。
The identification of the molecular mechanisms controlling cardiomyocyte proliferation during the embryonic, fetal, and early neonatal life appears of paramount interest in regard to exploiting this information to promote cardiac regeneration. Here, we show that the proliferative potential of neonatal rat cardiomyocytes is powerfully stimulated by the sustained activation of the Notch pathway. We found that Notch1 is expressed in proliferating ventricular immature cardiac myocytes (ICMs) both in vitro and in vivo, and that the number of Notch1-positive cells in the heart declines with age. Notch1 expression in ICMs paralleled the expression of its Jagged1 ligand on non-myocyte supporting cells. The inhibition of Notch signaling in ICMs blocked their proliferation and induced apoptosis; in contrast, its activation by Jagged1 or by the constitutive expression of its activated form using an adeno-associated virus markedly stimulated proliferative signaling and promoted ICM expansion. Maintenance or reactivation of Notch signaling in cardiac myocytes might represent an interesting target for innovative regenerative therapy.