Disease relevance of MMP1

• The 63- bp MMP1 promoter fragment -123 to -61 confers this FGF2 response on the rous sarcoma virus minimal promoter [1].
• This study examined the association between genotypes and haplotypes in the MMP1-MMP3-MMP12 gene cluster and risk of lung cancer development and metastasis [2].
• CONCLUSIONS: The observed multiple cancer-associated genetic variants suggested that the MMP1-MMP3-MMP12 gene cluster plays important roles in lung cancer development and progression [2].
• CONCLUSION: The reported association between the MMP1 promoter polymorphism and ovarian cancer risk was not supported by our data [3].
• We genotyped 100 women with endometriosis and 150 control subjects in North China. There was a significant difference in frequency of the MMP1 genotype between cases and controls (P=0.03) [4].
• These results suggest that MMP single-nucleotide polymorphisms influence breast cancer behavior and that the MMP-1 2G/2G genotype increases the risk of lymph node metastasis and predicts poor prognosis [5].

Psychiatry related information on MMP1

• Interestingly, elevated levels of MMP1 and MMP3 have been observed in the brains of Alzheimer's disease (AD) patients and those of tissue inhibitors of MMPs in the cerebrospinal fluid of AD and Parkinson's disease (PD) patients, suggesting a role for MMPs in these disorders [6].
• Preliminary findings suggest that abnormalities in matrix metalloproteinase (MMP) activity may be found in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD) [7].
• Our purpose was to determine the therapeutic efficacy of a selective-spectrum MMPI, ONO-4817 (inhibits MMP-2 and MMP-9 but not MMP-1), against established lung micrometastasis in combination with a cytotoxic anticancer drug, DOC, in a nude mouse model [8].
• Mononuclear phagocyte differentiation, activation, and viral infection regulate matrix metalloproteinase expression: implications for human immunodeficiency virus type 1-associated dementia [9].
• OBJECTIVE: The purpose of the present study was to investigate the effect of smoking cessation on the peripheral neutrophil mRNA expression levels for inflammatory cytokines, chemokine, growth factor and matrix metalloproteinase (MMP) [10].

High impact information on MMP1

• We show that histone deacetylase 7 (HDAC7) is specifically expressed in the vascular endothelium during early embryogenesis, where it maintains vascular integrity by repressing the expression of matrix metalloproteinase (MMP) 10, a secreted endoproteinase that degrades the extracellular matrix [11].
• The authors show that remodeling of the extracellular matrix by the matrix metalloproteinase MT1-MMP contributes to the three-dimensional development of white adipose tissue in mice [12].
• MMP-1 activity is derived from fibroblasts and is absent from the breast cancer cells [13].
• These results demonstrate that MMP-1 in the stromal-tumor microenvironment can alter the behavior of cancer cells through PAR1 to promote cell migration and invasion [13].
• We find that the matrix metalloproteinase, MT1-MMP, confers tumor cells with a distinct 3D growth advantage in vitro and in vivo [14].

Chemical compound and disease context of MMP1

• Inhibition of angiogenesis and metastasis in two murine models by the matrix metalloproteinase inhibitor, BMS-275291 [15].
• Neither THP was hydrolyzed by MMP-1, -3, -13, or -14. alpha1(V)436-447 fTHP and a general fluorogenic THP were used to screen for triple-helical peptidase activity in alpha(2)beta(1) integrin-stimulated melanoma cells [16].
• Glycine-extended gastrin induces matrix metalloproteinase-1- and -3-mediated invasion of human colon cancer cells through type I collagen gel and Matrigel [17].
• Phosphocitrate inhibits calcium hydroxyapatite induced mitogenesis and upregulation of matrix metalloproteinase-1, interleukin-1beta and cyclooxygenase-2 mRNA in human breast cancer cell lines [18].
• MMP-1 mRNA expression in the control group was significantly upregulated after the addition of tretinoin, whereas no significant change was observed in the keloid group [19].

Biological context of MMP1

• However, haplotypes consisting of alleles from the MMP1 G-1607GG and MMP12 Asn357Ser polymorphisms were associated with rate of decline of lung function (P = 0.0007) [20].
• These data suggest that polymorphisms in the MMP1 and MMP12 genes, but not MMP9, are either causative factors in smoking-related lung injury or are in linkage disequilibrium with causative polymorphisms [20].
• CONCLUSION: The results indicate that SAF-1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients [21].
• Transactivation of the MMP1 promoter by overexpressed Lf requires the presence of an AP-1 binding site [22].
• Here, using Affymetrix gene chip analysis, we show that reexpression of LGI1 in T98G cells results in the down-regulation of several MMP genes, in particular MMP1 and MMP3 [23].

Anatomical context of MMP1

• The activator appears to be associated with cell membranes and may be membrane-type matrix metalloproteinase 1(MT-MMP1) [24].
• In toto, these data indicate that PE1 participates in the transcriptional regulation of the MMP1 promoter in osteoblasts [25].
• A higher level of MMP1 mRNA was found in both control and treated MDA-MB-231 cells compared with the other two cell lines [26].
• METHODS: The MMP1 promoter polymorphism was examined in white blood cell DNA from 311 cases and 387 age- and race-matched controls using a radiolabeled polymerase chain reaction assay [3].
• Inhibition of JNK prevented MMP1 overexpression in oxidative stressed human tendon cells [27].

Associations of MMP1 with chemical compounds

• Inhibitors of protein kinase C, phosphatidyl inositol 3-OH kinase, and calmodulin-dependent protein kinase do not attenuate MMP1 promoter activation [1].
• A single guanine insertion polymorphism (2G) in the MMP1 promoter creates an Ets binding site that causes high levels of transcription and correlates with risk for some malignancies [28].
• In MDA-MB-231 cells, low concentrations of MMP1 protein were detected in medium from treated cells and was only significantly increased after 24 h but it was inhibited by cycloheximide [26].
• Phorbol myristate acetate, known to induce protease activity in other endothelial cell populations, stimulated MMP1, MMP9, and TIMP1 secretion in both NDEC and PEDEC [29].
• RESULTS: The glucocorticoids, dexamethasone, triamcinolone, and prednisolone, markedly decreased MMP1, MMP3, MMP13, TIMPI, and ferritin steady-state mRNA levels [30].

Physical interactions of MMP1

• The in vitro angiogenic activity of VEGF(165) blocked in the VEGF(165).CTGF complex was reactivated to original levels after CTGF digestion of the complex with MMP-1, -3, and -13 [31].
• It was suggested that G-Gly increased the number of vesicles containing MMP-1 and that MMP-1 interacted with CD147 to increase invasion [17].
• The MMP-1/TIMP-1 complex level was measured by an enzyme-linked immunosorbent assay kit [32].
• Our data highlight a new PPAR-gamma-dependent inhibitory mechanism on IL-1beta-mediated cartilage degradation occurring through DNA binding competition on the composite PPRE/AP1 site in the MMP1 promoter [33].
• Analysis of the signal transduction leading to activation of the MMP-1 gene revealed the presence of an OSM-responsive element (OMRE) encompassing the AP-1 binding site and the signal transducer and activator of transcription (STAT) binding element, which mediate activation by OSM [34].

Enzymatic interactions of MMP1

• MMP-2 cleaves at the same Gly-Ile/Leu bond in the collagen alpha chains as interstitial collagenases with kcat and Km values similar to that of MMP-1 [35].
• Experiments with intact type II collagen as well as a synthetic peptide suggested that MMP-13 cleaved type II collagen at the same bond as MMP-1, but this was then followed by a secondary cleavage that removed three amino acids from the 1/4 fragment amino terminus [36].
• Matrix metalloproteinase (MMP)-2 cleaves the 4 amino-terminal residues of the chemokine, stromal cell-derived factor (SDF)-1alpha, yielding a highly neurotoxic molecule, SDF(5-67), which fails to bind to its cognate receptor, CXCR4 [37].
• In this report, we have inserted the cDNA encoding the signal and propeptide sequences of MT1-MMP (MT(1-109)) and the cDNA encoding propeptide-deleted mature MT1-MMP (MT delta pro) in expression vectors that were then transfected into matrix metalloproteinase-deficient COS-1 cells [38].
• Several members of the matrix metalloproteinase family have been reported to cleave aggrecan in the interglobular domain between Asn-341 and Phe-342 [39].

Co-localisations of MMP1

• Confocal immunofluorescence and co-immunoprecipitation studies suggest that MMP-1 colocalized with alpha(2)beta(1) integrin on CXCL-12-stimulated NK-cell surface [40].
• Furthermore, EMMPRIN colocalized with MMP-1/collagenase-1 in the glandular epithelium in vivo [41].

Regulatory relationships of MMP1

• However, VEGF treatment significantly enhanced production of matrix metalloproteinase (MMP)-1, -3, and -9 by human SMCs [42].
• Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9 [43].
• Tumor necrosis factor-alpha (TNFalpha) and granulocyte macrophage colony-stimulating factor (GM-CSF) individually enhance monocyte matrix metalloproteinase-9 (MMP-9) but induce MMP-1 only when added in combination [44].
• Cyclooxygenase-2-derived E prostaglandins down-regulate matrix metalloproteinase-1 expression in fibroblast-like synoviocytes via inhibition of extracellular signal-regulated kinase activation [45].
• Oncostatin M stimulates monocyte chemoattractant protein-1- and interleukin-1-induced matrix metalloproteinase-1 production by human synovial fibroblasts in vitro [46].
• Purified Wnt-5A protein and transfection with Wnt-5A expression vector promoted the expression of MMP-1, MMP-3, MMP-9, and MMP-13 [47].

Other interactions of MMP1

• The upregulation of MMP-1 and MMP-9 was pronounced, and the stimulation for MMP-3 was less prominent [42].
• The activation of the extracellular signal-regulated kinase 1 (ERK1)/ERK2 (designated ERK1,2) pathway by oncogenic Ras, constitutively active Raf-1, or phorbol ester resulted in potent stimulation of MMP-1 promoter activity and mRNA expression [48].
• Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture [49]?
• PATIENTS AND METHODS: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC) [50].
• Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-11, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells [50].
• We also found that interleukin 6 (IL-6) released by fibroblasts was essential for the augmentation of MMP-1 expression by U937 macrophages [51].

Analytical, diagnostic and therapeutic context of MMP1

• METHODS: DNase I footprint and electrophoretic mobility shift assays were performed to identify active elements of the MMP1 promoter and the transcription factors that interact with it [21].
• Using laser microdissection, we extend our studies to the analysis of SMCs from LAM nodules where we observe higher MMP1 expression and MMP2 activation [52].
• MMP1 activity was measured using a spectrophotometric assay and western blotting [53].
• JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons was evaluated by immunohistochemistry [27].
• We investigated the relationship between the MMP1 polymorphism and ovarian cancer risk in a large population-based, case-control study [3].

References