Akt promotes increased cardiomyocyte cycling and expansion of the cardiac progenitor cell population
Akt promotes increased cardiomyocyte cycling and expansion of the cardiac progenitor cell population
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DOI：
10.1161/01.res.0000236754.21499.1c
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发表时间：
2006-08-18
影响因子：
20.1
通讯作者：
Sussman, Mark A.
中科院分区：
文献类型：
--
作者：
Gude, Natalie;Muraski, John;Sussman, Mark A.
在非心肌细胞中，Akt的激活与促进细胞周期和细胞增殖有关，但在心肌中这种核内Akt积聚的影响尚未被探索。核靶向Akt(Akt/nuc)在转基因动物中的心脏特异性表达延长了出生后细胞周期，在出生后2-3周Ki67(+)心肌细胞的数量增加就是证据。同样，核靶向Akt促进假定的心脏祖细胞种群的扩大，通过结合心肌细胞特异性标记Nkx 2.5或MEF2C的c-kit免疫标记进行评估。在核靶向Akt心肌样本中，发现促增殖细胞因子增加，包括肿瘤坏死超家族8、白细胞介素17e和肝细胞生长因子。Akt/nuc表达下游旁分泌因子介导的并发信号可能与核靶向Akt在心肌中的表型效应有关，包括促进细胞增殖和干细胞数量的扩大。
Activation of Akt is associated with enhanced cell cycling and cellular proliferation in nonmyocytes, but this effect of nuclear Akt accumulation has not been explored in the context of the myocardium. Cardiac-specific expression of nuclear-targeted Akt (Akt/nuc) in transgenics prolongs postnatal cell cycling as evidenced by increased numbers of Ki67(+) cardiomyocytes at 2 to 3 weeks after birth. Similarly, nuclear-targeting of Akt promotes expansion of the presumptive cardiac progenitor cell population as assessed by immunolabeling for c-kit in combination with myocyte-specific markers Nkx 2.5 or MEF 2C. Increases in pro-proliferative cytokines, including tumor-necrosis superfamily 8, interleukin-17e, and hepatocyte growth factor, were found in nuclear-targeted Akt myocardial samples. Concurrent signaling mediated by paracrine factors downstream of Akt/nuc expression may be responsible for phenotypic effects of nuclear-targeted Akt in the myocardium, including enhanced cell proliferation and expansion of the stem cell population.