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Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1

  • Authors:
    • Haibin Gong
    • Xiuli Wang
    • Lei Wang
    • Ying Liu
    • Jie Wang
    • Qian Lv
    • Hui Pang
    • Qinglin Zhang
    • Zhenquan Wang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Xuzhou Central Hospital, Xuzhou Cardiovascular Disease Institute, Xuzhou, Jiangsu 221009, P.R. China
    Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 787-793
    |
    Published online on: May 26, 2017
       https://doi.org/10.3892/mmr.2017.6639
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Abstract

Bone marrow mesenchymal stem cells (BMSCs) have the potential to transdifferentiate into cardiomyocyte‑like cells (CLCs) if an appropriate cardiac environment is provided. Insulin‑like growth factor‑1 (IGF‑1) plays an important role in the cell migration, survival and differentiation of BMSCs. However, the effect of IGF‑1 on the cellular differentiation remains unclear. In the present study, BMSCs were isolated from rat femurs and tibias and the cells were purified at passage 6 (P6). IGF‑1 and IGF‑1 receptor (IGF‑1R) kinase inhibitor I‑OMe AG538 were added to detect if IGF‑1 could induce BMSCs to transdifferentiate into CLCs and if I‑OMe AG538 could inhibit IGF‑1‑mediated receptor activation and downstream signaling. Immunostaining demonstrated that all P6 BMSCs express CD29 and CD44 but not CD45. BMSCs induced by 15 ng/ml IGF‑1 revealed positivity for cardiac troponin‑T and cardiac troponin‑I. The optimal induction time was 14 days but the expression of these proteins were incompletely inhibited by 300 nmol/l I‑OMe AG538 and completely inhibited by 10 µmol/l I‑OMe AG538. Western blotting showed that the level of IGF‑1R autophosphorylation and the expression of cTnT and cTnI were higher when BMSCs were induced for 14 days. I‑OMe AG538 selectively inhibited IGF‑1‑mediated growth and signal transduction and the inhibitory effect of I‑OMe AG538 were not reverted in the presence of exogenous IGF‑1. In addition, when a time course analysis of the effects of I‑OMe AG538 on mitogen‑activated protein kinase kinase and phosphatidylinositol 3‑kinase signaling were done, we observed a transient inhibitory effect on Erk1/2 and Akt phosphorylation, in keeping with the inhibitory effects on cell growth. Taken together, these data indicate that I‑OMe AG538 could inhibit IGF-1-induced CLCs in BMSCs and this effect is time- and concentration-dependent.
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Copy and paste a formatted citation
Spandidos Publications style
Gong H, Wang X, Wang L, Liu Y, Wang J, Lv Q, Pang H, Zhang Q and Wang Z: Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Mol Med Rep 16: 787-793, 2017.
APA
Gong, H., Wang, X., Wang, L., Liu, Y., Wang, J., Lv, Q. ... Wang, Z. (2017). Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Molecular Medicine Reports, 16, 787-793. https://doi.org/10.3892/mmr.2017.6639
MLA
Gong, H., Wang, X., Wang, L., Liu, Y., Wang, J., Lv, Q., Pang, H., Zhang, Q., Wang, Z."Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1". Molecular Medicine Reports 16.1 (2017): 787-793.
Chicago
Gong, H., Wang, X., Wang, L., Liu, Y., Wang, J., Lv, Q., Pang, H., Zhang, Q., Wang, Z."Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1". Molecular Medicine Reports 16, no. 1 (2017): 787-793. https://doi.org/10.3892/mmr.2017.6639
Copy and paste a formatted citation
x
Spandidos Publications style
Gong H, Wang X, Wang L, Liu Y, Wang J, Lv Q, Pang H, Zhang Q and Wang Z: Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Mol Med Rep 16: 787-793, 2017.
APA
Gong, H., Wang, X., Wang, L., Liu, Y., Wang, J., Lv, Q. ... Wang, Z. (2017). Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Molecular Medicine Reports, 16, 787-793. https://doi.org/10.3892/mmr.2017.6639
MLA
Gong, H., Wang, X., Wang, L., Liu, Y., Wang, J., Lv, Q., Pang, H., Zhang, Q., Wang, Z."Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1". Molecular Medicine Reports 16.1 (2017): 787-793.
Chicago
Gong, H., Wang, X., Wang, L., Liu, Y., Wang, J., Lv, Q., Pang, H., Zhang, Q., Wang, Z."Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1". Molecular Medicine Reports 16, no. 1 (2017): 787-793. https://doi.org/10.3892/mmr.2017.6639
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