EMMPRIN mediates matrix metalloproteinase 9 expression and monocyte migration: evidence from EMMPRIN knockdown by RNA interference

AIM: Although the evidence indicates that extracellular matrix metalloproteinase inducer (EMMPRIN) is closely associated with matrix metalloproteinase (MMP) expression in tumor cells, tumor invasion and metastasis, no direct proof that EMMPRIN regulates MMPs in monocytes, especially in the atherogenic milieu is observed. Here we tested this hypothesis by examining MMP-9 expression in macrophages/foam cells and monocyte migration through EMMPRIN knockdown by siRNA. METHODS: The methods of qPCR and Western blotting were used to detect the suppressions of EMMPRIN mRNA and protein expression in macrophages and foam cells transfected with EMMPRIN-specific siRNA. The protein expression of MMP-9 in macrophages and foam cells was also determined. Monocyte migration after EMMPRIN knockdown was observed by a Transwell assay. RESULTS: EMMPRIN knockdown by siRNA markedly abolished the MMP-9 expression by 50% and 40% in macrophages and foam cells, respectively. Migration induced by chemotactic factor MCP-1 and VEGF was significantly attenuated (P<0.05) in monocytes treated with EMMPRIN-siRNA. CONCLUSION: The protein expression and secretion of MMP-9 are down-regulated by EMMPRIN knockdown during monocyte differentiation into macrophages and foam cells. Moreover, EMMPRIN siRNA treatment also prevents monocyte migration. Thus, EMMPRIN plays a key regulatory role for MMP activity and monocyte migration, making it a potential target for pharmacological intervention of atherosclerosis.