›› 2009, Vol. 29 ›› Issue (9): 1057-.

• Original article (Basic research) • Previous Articles     Next Articles

Effects and mechanism of visfatin on MMP-9 in macrophages

FAN Yu-qi, HE Ben, WANG Bin-yao   

  1. Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China
  • Online:2009-09-25 Published:2009-09-29


Objective To investigate the effects and mechanism of visfatin on matrix metalloproteinases-9 (MMP-9) expression and invasive activity in macrophages. Methods THP-1 monocytes were induced into macrophages. To investigate the effects of visfatin on MMP-9, cells were divided into 2 groups: ①macrophages+visfatin 12 h;②macrophages+visfatin 24 h. The concentrations of visfatin in each group were:0(control), 50, 100, 200, 400 ng/mL. MMP-9 mRNA and protein expression were analysed by RT-PCR and Western blotting, and MMP-9 invasive activity was assayed by gelatin zymography. To investigate the mechanism of visfatin on MMP-9, cells were divided into 5 groups: ①macrophages without stimulation (control); ②macrophages pretreated with MAPK p38, ERK1/2, JNK pathway inhibitor for 1 h, then stimulated with visfatin (200 ng/mL)for 24 h; ③macrophages pretreated with retinoid X receptors (RXR) nature ligand or peroxisome proliferators activated receptor γ (PPARγ) natural/synthetic ligand for 1 h,then stimulated with visfatin(200 ng/mL)for 24 h; ④macrophages stimulated with visfatin (200 ng/mL) for 24 h; ⑤macophages+visfatin (200 ng/mL)for different time(5, 10, 15, 30, 60 min). MMP-9 expression, PPARγ expression, and the effect of visfatin on MAPK phosphorylation were analysed by Western blotting. Results Visfatin not only significantly enhanced MMP-9 mRNA and protein expression in macrophages(P<0.05, P<0.01), but also up-regulated MMP-9 invasive activity(P<0.01). p38 MAPK inhibitor, ERK1/2 MAPK inhibitor and RXR ligand significantly blocked visfatin activity. Visfatin activated the phosphorylation of p38 MAPK and ERK1/2 MAPK, while had no effect on expression of PPARγ protein. Conclusion Visfatin enhances inflammatory factors expression and activity in macrophages which is related with ERK1/2 MAPK and p38 MAPK, and RXR may mediate visfatin activity.

Key words: visfatin, matrix metalloproteinase, mitogen-activated protein kinase, retinoid X receptors, atherosclerosis

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