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Ann Mary, Johnson and C. C., Kartha (2014) Proliferation of murine c-kitpos cardiac stem cells stimulated with IGF-1 is associated with Akt-1 mediated phosphorylation and nuclear export of FoxO3a and its effect on downstream cell cycle regulators. Growth factors (Chur, Switzerland), 32 (2). pp. 53-62. ISSN 1029-2292

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Insulin-like growth factor-1 (IGF-1) is known to promote proliferation in many cell types including c-kitpos cardiac stem cells (CSCs). Downstream signaling pathways of IGF-1 induced CSC proliferation have not been investigated. An important downstream target of IGF-1/Akt-1 signaling is FoxO3a, a key negative regulator of cell-cycle progression. We studied the effect of IGF-1 on proliferation of c-kitpos murine CSCs and found that IGF-1-mediated cell proliferation is associated with FoxO3a phosphorylation and inactivation of its transcriptional activity. PI3 inhibitors LY294002 and Wortmannin abolished the effect of IGF-1 on FoxO3a phosphorylation indicating that FoxO3a phosphorylation is mediated by PI3/Akt-1 pathway. In cells with FoxO3a translocation to the cytoplasm, there is decreased expression of cell-cycle inhibitors such as p27kip1 and p57kip2 and increased expression of CyclinD1. Our study provides evidence that IGF-1 induced CSC proliferation could be the result of FoxO3a inactivation and its downstream effect on cell-cycle regulators.

Item Type: Article
Uncontrolled Keywords: Akt-1, cell-cycle inhibitors, cardiac stem cells, FoxO3a, insulin-like growth factor
Subjects: Cardiovascular Diseases And Diabetes Biology
Depositing User: Rgcb Library
Date Deposited: 03 Jul 2017 07:39
Last Modified: 03 Jul 2017 07:39
URI: http://rgcb.sciencecentral.in/id/eprint/382

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