The Role of Zinc Binding Protein-89 (ZBP-89) in Basal and IL-1 Induced Expression of Matrix Metalloproteinase-3 (MMP-3)

MMP-3 plays an important role in normal and pathological tissue remodeling. Its expression is regulated by a variety of cytokines, growth factors, and hormones, mainly at the transcriptional level. Transcription factor ZBP-89 has been shown to interact with a polymorphic promoter sequence and activate transcription of the MMP-3 gene when overexpressed. To examine the role of ZBP-89 in basal and IL-1 induced expression of MMP-3, ZBP-89 was stably knocked down in MG-63 cells and MMP-3 mRNA expression was measured by real-time PCR. The basal expression of MMP-3 was significantly lower in the knock-down cell line in comparison to negative control cells. This is consistent with a role for ZBP-89 as an activator of basal expression. IL-1 fold induction was significantly higher at 6 hours in the knock-down cell line. This is consistent with a role of ZBP-89 as a repressor of IL-1 induced expression of MMP-3.