Macrophage migration inhibitory factor promotes cardiac fibroblast proliferation through the Src kinase signaling pathway

  • Authors:
    • Yu‑Mei Xue
    • Chun‑Yu Deng
    • Wei Wei
    • Fang‑Zhou Liu
    • Hui Yang
    • Yang Liu
    • Xin Li
    • Zhaoyu Wang
    • Su‑Juan Kuang
    • Shu‑Lin Wu
    • Fang Rao
  • View Affiliations

  • Published online on: December 12, 2017     https://doi.org/10.3892/mmr.2017.8261
  • Pages: 3425-3431
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Abstract

Atrial fibrosis is the fundamental characteristic of the structural pathology associated with atrial fibrillation (AF). Inflammation can contribute to atrial fibrosis, engendering AF. The present study aimed to investigate the role of macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, in the regulation of proliferation and function of cardiac fibroblasts (CFs). Biochemical assays were performed to examine the expression of extracellular matrix (ECM) in human atrial tissues, and the proliferation and regulation of ECM induced by MIF in CFs. The expression of ECM, including collage type 3, α1 (Col‑3A1), matrix metalloproteinase (MMP)‑2/-9 and transforming growth factor (TGF)‑β was higher in patients with permanent AF, compared with patients in sinus rhythm (SR), and the expression levels of MIF were also increased in AF. Treatment of CFs with mouse recombinant MIF (rMIF; 40 nM) for 48 h was found to promote the proliferation of CFs. The MIF‑induced CF proliferation was completely inhibited by tyrosine kinase inhibitor‑PP1. rMIF treatment also stimulated the activation of Src kinase in CFs. In addition, MIF treatment upregulated the expression levels of fibrosis‑related proteins, Col‑1, Col‑3, MMP‑2/-9 and TGF‑β, in the CFs. These results suggested that MIF was involved in the structural remodeling that accompanies AF, possibly by promoting the proliferation of CFs and increasing the expression of ECM. These data implicate inflammation as a potential driver of CF.
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February-2018
Volume 17 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Xue YM, Deng CY, Wei W, Liu FZ, Yang H, Liu Y, Li X, Wang Z, Kuang SJ, Wu SL, Wu SL, et al: Macrophage migration inhibitory factor promotes cardiac fibroblast proliferation through the Src kinase signaling pathway. Mol Med Rep 17: 3425-3431, 2018
APA
Xue, Y., Deng, C., Wei, W., Liu, F., Yang, H., Liu, Y. ... Rao, F. (2018). Macrophage migration inhibitory factor promotes cardiac fibroblast proliferation through the Src kinase signaling pathway. Molecular Medicine Reports, 17, 3425-3431. https://doi.org/10.3892/mmr.2017.8261
MLA
Xue, Y., Deng, C., Wei, W., Liu, F., Yang, H., Liu, Y., Li, X., Wang, Z., Kuang, S., Wu, S., Rao, F."Macrophage migration inhibitory factor promotes cardiac fibroblast proliferation through the Src kinase signaling pathway". Molecular Medicine Reports 17.2 (2018): 3425-3431.
Chicago
Xue, Y., Deng, C., Wei, W., Liu, F., Yang, H., Liu, Y., Li, X., Wang, Z., Kuang, S., Wu, S., Rao, F."Macrophage migration inhibitory factor promotes cardiac fibroblast proliferation through the Src kinase signaling pathway". Molecular Medicine Reports 17, no. 2 (2018): 3425-3431. https://doi.org/10.3892/mmr.2017.8261