Study summary · research use only
Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study of fetal sheep cardiomyocytes, the authors tested whether insulin-like growth factor-1 (IGF-1) acts through the ERK and PI3K signaling pathways. Long R3 IGF-1 given in vivo did not stimulate cardiomyocyte hypertrophy but was associated with a decreased percentage of binucleated cells. In culture, LR3 IGF-1 increased bromodeoxyuridine uptake by three- to five-fold, and this uptake was abolished when either ERK or PI3K signaling was blocked (by UO-126 or LY-294002). The authors report that LR3 IGF-1 did not increase footprint area or binucleation, and conclude that IGF-1 through its receptor stimulated cardiomyocyte division requiring both ERK and PI3K, without stimulating hypertrophy in vivo or in vitro.
Abstract
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.
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