Premium
The role of human macrophage migration inhibitory factor in promoting angiogenesis
Author(s) -
Yu XiYong,
Shan ZhiXin,
Lin QiuXiong,
Cai ShiXia,
Yang Min,
Lin ShuGuang
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a652
Subject(s) - macrophage migration inhibitory factor , angiogenesis , neovascularization , in vivo , microbiology and biotechnology , in vitro , vascular endothelial growth factor , immunohistochemistry , endothelial stem cell , macrophage , cell migration , chemistry , biology , immunology , cancer research , cytokine , biochemistry , vegf receptors
OBJECTIVE The rupture mechanisms of atherosclerotic plaque may involve the neovascularization in vulnerable plaque. The present study is to study the potential role of Macrophage migration inhibitory factor (MIF) in promoting angiogenesis. METHODS For in vitro study, the human vascular endothelial cell was cultured and incubated with MIF, VEGF and BSA on ECMatrix gel, then the visual patterns of tube formation were observed. For in vivo study, Matrix gel mixed with or without MIF and heparin was subcutaneouly injected into BALB/c mice, and the ECMatrix plug was peeled off and identified by immunohistochemical analysis. The vascular endothelial cells were also incubated with or without MIF for 6 or 24 hours, the mRNA was used to study the angiogenetic genes expression by using DNA microarray technique, and the protein extracts were used to study phosphorylated‐ERK1 / total ERK1 protein level by western blotting. RESULTS The tube formation of endothelial cells induced by MIF was in does‐dependent manner in vitro, significantly at 50 ng/ml. The factor vWF immunohistochemical analysis showed that MIF could promote the blood vessels formation in ECMatrix gel plug in vivo( p<0.05 ). Among all 96 angiogenetic genes tested, MIF could up‐regulate 34 angiogenetic genes expression in endothelial cells specifically, such as CGA,FGF1,FGFR3,VEGF‐D/F,MMP‐9, PDGF, Smad1 and so on, this results can be repeated by RT‐PCR. MIF also promotes phosphorylation protein level in time‐dependent way. CONCLUSION MIF could promote endothelial cells angiogenesis in vitro and in vivo by up‐regulating angiogenetic factor genes expression in vascular endothelial cells. (This work was supported by grants from Guangdong Provincial Natural Science Foundation for Research Team No.015015,033189)