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Macrophage migration inhibitory factor promotes cardiac fibroblast proliferation through the Src kinase signaling pathway.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2018 Feb; Vol. 17 (2), pp. 3425-3431. Date of Electronic Publication: 2017 Dec 12. - Publication Year :
- 2018
-
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.
- Subjects :
- Adult
Animals
Arrhythmia, Sinus metabolism
Atrial Fibrillation metabolism
Collagen analysis
Collagen metabolism
Extracellular Matrix metabolism
Extracellular Matrix pathology
Female
Fibroblasts metabolism
Heart Atria metabolism
Heart Atria pathology
Humans
Intramolecular Oxidoreductases analysis
Macrophage Migration-Inhibitory Factors analysis
Male
Matrix Metalloproteinase 2 analysis
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 analysis
Matrix Metalloproteinase 9 metabolism
Mice
Middle Aged
Arrhythmia, Sinus pathology
Atrial Fibrillation pathology
Cell Proliferation
Fibroblasts pathology
Intramolecular Oxidoreductases metabolism
Macrophage Migration-Inhibitory Factors metabolism
Signal Transduction
src-Family Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 29257298
- Full Text :
- https://doi.org/10.3892/mmr.2017.8261