Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplastic transformation mediated by ras oncogenes is associated with deregulated expression of genes encoding, for example, various proteases, lysyl oxidase, and smooth-muscle alpha-actin. To define the role of these genes in the initiation or maintenance of the ras-transformed state, we compared their steady-state mRNA levels in two different sets of preneoplastic fibroblast lines, ras-transformed clones, and phenotypic revertants derived from them. Compared with the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix metalloproteinase-3), and collagenase I (matrix metalloproteinase-1) mRNA but undetectable levels of lysyl oxidase mRNA. Partial restoration of lysyl oxidase transcription was observed in four of five phenotypic revertants derived from rat FE-8 and NIHpEJcl3 cells. The elevated levels of transin mRNA found in NIHpEJcl3 cells were diminished to the pretransformation level in interferon revertants but were not reduced in phenotypic rat FE-8 revertants expressing a high level of the ras oncoprotein. High steady-state levels of collagenase I mRNA were dependent on ras expression but were not closely associated with the transformed phenotype. High levels of cathepsin L mRNA were associated with neither high ras expression nor neoplastic transformation. The downregulation of smooth-muscle alpha-actin, characteristic of transformed cell lines, was not reversible in phenotypic revertants.
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PMID:Partial restoration of pre-transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants. 772 41

Temporal and topographic expression of matrix metalloproteinases (MMPs) after perivascular electric injury was studied in wild-type (WT) and urokinase-deficient (u-PA-/-) mice. Neointima formation after injury of the femoral artery was significantly reduced in u-PA-/- mice as compared to WT mice (area of 0.002+/-0.0007 mm2 versus 0.008 + 0.002 mm2 at 3 weeks after injury; p <0.001), associated with impaired cellular migration (nuclear cell counts of 44+/-5 versus 82+/-9in cross-sectional areas; p <0.001). Zymographic and/or microscopic analysis indicated that MMP expression gradually increased to reach a maximum at 1 to 2 weeks after vascular injury. In general, MMP levels were lower in u-PA-/- than in WT mice. In non-injured arteries, MMP-2 (gelatinase A) and MMP-3 (stromelysin-1) were produced mainly by adventitial fibroblasts and/or non-contractile smooth muscle cells (SMC). One week after injury, MMP-2 and MMP-3 levels were enhanced due to an increased number and size of producing cells; 2 to 3 weeks after injury, MMP-2 and MMP-3 were produced also by some contractile SMC, which stained with alpha-actin antiserum. MMP-9 (gelatinase B), MMP-12 (metalloelastase) and MMP-13 (collagenase-3) were found in macrophages located mainly in the adventitia. Immunogold electron microscopic examination revealed that MMP-2 was located predominantly in association with the cell surface of fibroblasts or SMC, while MMP-9 and MMP- 12 were located in well defined storage granules within macrophages. MMP-2, MMP-3 and MMP-13, but not MMP-9 or MMP-12, were also found extracellularly, associated with elastin-containing structures (MMP-2), with the basement membrane and occasionally with collagen fibres (MMP-3), or with proteoglycans, collagen and elastin (MMP-13). The temporal and topographic expression pattern of MMPs after vascular injury, coinciding with smooth muscle cell migration and neointima formation, thus is compatible with a role in vascular remodeling.
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PMID:Temporal and topographic matrix metalloproteinase expression after vascular injury in mice. 1036 56