Open AccessMacrophage migration inhibitory factor promotes cardiac fibroblast proliferation through the Src kinase signaling pathway
Author(s) -
Yumei Xue,
Chunyu Deng,
Wei Wei,
FangZhou Liu,
Hui Yang,
Yang Liu,
Xin Li,
Zhaoyu Wang,
SuJuan Kuang,
Shulin Wu,
Fang Rao
Publication year - 2017
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2017.8261
Subject(s) - macrophage migration inhibitory factor , inflammation , fibrosis , signal transduction , biology , transforming growth factor , microbiology and biotechnology , cancer research , proto oncogene tyrosine protein kinase src , tyrosine kinase , kinase , cytokine , immunology , medicine
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.