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首页> 外文期刊>American Journal of Physiology >Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes.
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Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes.

机译：细胞外信号调节激酶和磷酸肌醇3激酶介导IGF-1诱导胎羊心肌细胞增殖。

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摘要

Growth of the fetal heart involves cardiomyocyte enlargement, division, and maturation. Insulin-like growth factor-1 (IGF-1) is implicated in many aspects of growth and is likely to be important in developmental heart growth. IGF-1 stimulates the IGF-1 receptor (IGF1R) and downstream signaling pathways, including extracellular signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K). We hypothesized that IGF-1 stimulates cardiomyocyte proliferation and enlargement through stimulation of the ERK cascade and stimulates cardiomyocyte differentiation through the PI3K cascade. In vivo administration of Long R3 IGF-1 (LR3 IGF-1) did not stimulate cardiomyocyte hypertrophy but led to a decreased percentage of cells that were binucleated in vivo. In culture, LR3 IGF-1 increased myocyte bromodeoxyuridine (BrdU) uptake by three- to five-fold. The blockade of either ERK or PI3K signaling (by UO-126 or LY-294002, respectively) completely abolished BrdU uptake stimulated by LR3 IGF-1. LR3 IGF-1 did not increase footprint area, but as expected, phenylephrine stimulated an increase in binucleated cardiomyocyte size. We conclude that 1) IGF-1 through IGF1R stimulates cardiomyocyte division in vivo; hyperplastic growth is the most likely explanation of IGF-1 stimulated heart growth in vivo; 2) IGF-1 through IGF1R does not stimulate binucleation in vitro or in vivo; 3) IGF-1 through IGF1R does not stimulate hypertrophy either in vivo or in vitro; and 4) IGF-1 through IGF1R requires both ERK and PI3K signaling for proliferation of near-term fetal sheep cardiomyocytes in vitro.
机译：胎儿心脏的生长涉及心肌细胞的扩大，分裂和成熟。胰岛素样生长因子-1（IGF-1）与生长的许多方面有关，可能在心脏发育中很重要。 IGF-1刺激IGF-1受体（IGF1R）和下游信号通路，包括细胞外信号调节激酶（ERK）和磷酸肌醇3激酶（PI3K）。我们假设IGF-1通过刺激ERK级联刺激心肌细胞增殖和扩增，并通过PI3K级联刺激心肌细胞分化。 Long R3 IGF-1（LR3 IGF-1）的体内给药并未刺激心肌肥大，但导致体内双核细胞百分比降低。在培养中，LR3 IGF-1使肌细胞溴脱氧尿苷（BrdU）摄取增加三到五倍。对ERK或PI3K信号的阻断（分别由UO-126或LY-294002阻断）完全消除了LR3 IGF-1刺激的BrdU摄取。 LR3 IGF-1不会增加足迹面积，但是正如预期的那样，去氧肾上腺素刺激了双核心肌细胞大小的增加。我们得出以下结论：1）IGF-1至IGF1R在体内刺激心肌细胞分裂;增生性生长是IGF-1刺激体内心脏生长的最可能解释; 2）IGF-1至IGF1R在体外或体内均不刺激双核化; 3）IGF-1至IGF1R在体内或体外均不刺激肥大; 4）IGF-1至IGF1R既需要ERK信号，又需要PI3K信号，才能在体外使近期胎羊心肌细胞增殖。

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