Disease relevance of MT1-MMP

• These results implicate PI3K-dependent regulation of MT1-MMP protein synthesis and subsequent activation of latent MMP-2 as critical events in neointimal hyperplasia after vascular injury [1].
• At peak ischemia, MT1-MMP activity was increased by >40% in the ischemic region, with no change in the remote region, which persisted with reperfusion (P<0.05) [2].
• Furthermore, in an isolated left ventricular myocyte model of I/R, hypoxia (simulated ischemia) induced a >70% increase in MT1-MMP abundance in myocytes, and confocal microscopy revealed MT1-MMP internalization during this time period and reemergence to the membrane with reperfusion [2].
• To understand the induction mechanism of MMP-14 under atherogenic conditions, we examined its expression pattern in response to oxidized low-density lipoproteins (ox-LDLs) that are believed to play an important role in atherogenesis [3].

High impact information on MT1-MMP

• In the present study, we have further purified to homogeneity a deletion mutant of MT1-MMP lacking the transmembrane domain (DeltaMT1) and native MT1-MMP secreted from a human breast carcinoma cell line (MDA-MB-231 cells) and examined their substrate specificities [4].
• Wortmannin blocked the MMP-2 but not the MMP-14 increase [5].
• In contrast, balloon angioplasty induced a significant increase in the levels of MT1-MMP, which was suppressed by LY-294002 [1].
• With the use of a confocal microscopy, membrane type-1 MMP (MT1-MMP) was localized to porcine LV myocytes, and immunoblotting for MT1-MMP using LV myocyte extracts revealed that after exposure to Iso, ET-1, ANG II, or PMA (P < 0.05), MT1-MMP abundance increased over 50% [6].
• The expression of MT1-MMP was also affected by bradykinin treatment [7].

Biological context of MT1-MMP

• A porcine MT1-MMP cDNA composed of 3284 bp was isolated from an enamel organ-specific cDNA library [8].
• Increased binding of SAF-1 to the MMP-14 promoter correlated with the transcriptional upregulation of MMP-14 gene [3].

Anatomical context of MT1-MMP

• Thus, we asked if MT1-MMP was also expressed by the cells responsible for the formation of enamel and dentin [8].
• In the enamel organs, however, the MT1-MMP message level became reduced only during the late secretory stage [8].
• Immunohistochemical analysis showed that MT1-MMP was present on the surface of the cells (ameloblasts and odontoblasts) responsible for dentin and enamel formation [8].
• Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane bound member of the MMP gene family that has previously been shown to be expressed by cells associated with bone and cartilage formation (osteoclasts, osteoblasts and chondrocytes) [8].
• METHODS AND RESULTS: Pigs (30 kg, n=8) were instrumented with microdialysis catheters to measure MT1-MMP activity in both ischemic and nonischemic (remote) myocardium [2].

Associations of MT1-MMP with chemical compounds

• No change in MT1-MMP mRNA was observed with LY-294002, because equivalent amounts of this mRNA were present in both injured and noninjured vessels [1].
• The wortmannin sensitivity implicates phosphoinositide 3-kinase as a modulator of the MMP-2 but not the MMP-14 increase [5].

Other interactions of MT1-MMP

• Activation of MMP-2 in response to vascular injury is mediated by phosphatidylinositol 3-kinase-dependent expression of MT1-MMP [1].

Analytical, diagnostic and therapeutic context of MT1-MMP

• Multiple tissue Northern blot analysis revealed that the MT1-MMP message was expressed highly in the enamel organ and pulp organ when compared to the expression levels observed in other non-mineralizing tissues [8].
• Differential centrifugation revealed that the endosomal fraction (which contains subcellular organelles) within the ischemic myocardium was associated with a >135% increase in MT1-MMP (P<0.05) [2].

References