Open Access

Macrophage migration inhibitory factor promotes cardiac stem cell proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK pathways

  • Authors:
    • Jinjin Cui
    • Fengyun Zhang
    • Yongshun Wang
    • Jingjin Liu
    • Xing Ming
    • Jingbo Hou
    • Bo Lv
    • Shaohong Fang
    • Bo Yu
  • View Affiliations

  • Published online on: March 29, 2016     https://doi.org/10.3892/ijmm.2016.2542
  • Pages: 1299-1309
  • Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophage migration inhibitory factor (MIF) has pleiotropic immune functions in a number of inflammatory diseases. Recent evidence from expression and functional studies has indicated that MIF is involved in various aspects of cardiovascular disease. In this study, we aimed to determine whether MIF supports in vitro c-kit+CD45- cardiac stem cell (CSC) survival, proliferation and differentiation into endothelial cells, as well as the possible mechanisms involved. We observed MIF receptor (CD74) expression in mouse CSCs (mCSCs) using PCR and immunofluorescence staining, and MIF secretion by mCSCs using PCR and ELISA in vitro. Increasing amounts of exogenous MIF did not affect CD74 expression, but promoted mCSC survival, proliferation and endothelial differentiation. By contrast, treatment with an MIF inhibitor (ISO-1) or siRNA targeting CD74 (CD74‑siRNA) suppressed the biological changes induced by MIF in the mCSCs. Increasing amounts of MIF increased the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which are known to support cell survival, proliferation and differentiation. These effects of MIF on the mCSCs were abolished by LY294002 [a phosphoinositide 3-kinase (PI3K) inhibitor] and MK-2206 (an Akt inhibitor). Moreover, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation increased following treatment with MIF. The AMPK inhibitor, compound C, partly blocked the pro-proliferative effects of MIF on the mCSCs. In conclusion, our results suggest that MIF promotes mCSC survival, proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK signaling pathways. Thus, MIF may prove to be a potential therapeutic factor in the treatment of heart failure and myocardial infarction by activating CSCs.
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May-2016
Volume 37 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Cui J, Zhang F, Wang Y, Liu J, Ming X, Hou J, Lv B, Fang S and Yu B: Macrophage migration inhibitory factor promotes cardiac stem cell proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK pathways. Int J Mol Med 37: 1299-1309, 2016.
APA
Cui, J., Zhang, F., Wang, Y., Liu, J., Ming, X., Hou, J. ... Yu, B. (2016). Macrophage migration inhibitory factor promotes cardiac stem cell proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK pathways. International Journal of Molecular Medicine, 37, 1299-1309. https://doi.org/10.3892/ijmm.2016.2542
MLA
Cui, J., Zhang, F., Wang, Y., Liu, J., Ming, X., Hou, J., Lv, B., Fang, S., Yu, B."Macrophage migration inhibitory factor promotes cardiac stem cell proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK pathways". International Journal of Molecular Medicine 37.5 (2016): 1299-1309.
Chicago
Cui, J., Zhang, F., Wang, Y., Liu, J., Ming, X., Hou, J., Lv, B., Fang, S., Yu, B."Macrophage migration inhibitory factor promotes cardiac stem cell proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK pathways". International Journal of Molecular Medicine 37, no. 5 (2016): 1299-1309. https://doi.org/10.3892/ijmm.2016.2542