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

Stromelysin and stromelysin 2, closely related members of the metalloproteinase gene family degrade many non-collagenous components of the extracellular matrix and may play a role in the activation of latent procollagenase. Because we use monolayer cultures of rabbit and human fibroblasts as model systems to study these enzymes, we compared their expression in fibroblasts from both species. Rabbit stromelysin purified from fibroblast culture medium often appears as a protein doublet, while human stromelysin is a single protein band. Hybrid selection with a cDNA clone for rabbit stromelysin and in vitro translation of mRNA from rabbit fibroblasts stimulated with phorbol myristate acetate (PMA) reveals two translation products, Mr54 and 56KD, as measured by SDS polyacrylamide gel electrophoresis. In vitro transcription and translation of a 1.8 kb cDNA for rabbit stromelysin gives a single protein product, preprostromelysin, MR 56KD. We do not yet know whether the rabbit doublet represents two distinct gene products or whether it results from posttranscriptional/posttranslational processing of a single transcript or protein. To study human stromelysin, we cloned a cDNA from a rheumatoid synovial cell cDNA library and we used it to isolate genes for stromelysin and a related gene, stromelysin-2. Both genes are contained on approximately 14 kilobase pairs of DNA. With an exon containing fragment of the human stromelysin-2 genomic clone as a specific probe in Northern blot analysis, we demonstrate the differential expression of stromelysin and stromelysin 2 in rheumatoid synovial cells, human foreskin fibroblasts, and rabbit synovial fibroblasts. Chimeric constructs containing 302 bp of the human stromelysin promoter DNA linked to the bacterial gene chloramphenicol acetyl transferase (CAT) can be induced by PMA, epidermal growth factor (EGF) and interleukin-1 beta (IL-1 beta). Since the genes for stromelysin and stromelysin 2 are so conserved and since mechanisms regulating their expression appear to be distinctive, identification of these mechanisms in both rabbits and humans will increase our understanding of the relative role of these enzymes in normal and disease processes.
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PMID:Expression of stromelysin and stromelysin-2 in rabbit and human fibroblasts. 148 18

Stromelysin is a member of a gene family of metalloproteinases involved in extracellular matrix remodeling in normal and diseased processes. Primary cultures of rheumatoid synovial cells produce large amounts of metalloproteinase mRNA and proteins. We cloned a cDNA for human stromelysin from a rheumatoid synovial cell cDNA library, and we used the cDNA to isolate the gene for human stromelysin and a related gene, stromelysin 2. We sequenced parts of the genes and found that both are contained on approximately 14 kilobase pairs of DNA. Using an exon-containing fragment of the stromelysin 2 genomic clone as a specific probe in Northern blot analysis, we demonstrate the differential expression of stromelysin and stromelysin 2 in rheumatoid synovial cells, human foreskin fibroblasts, and rabbit synovial fibroblasts. In addition, using chimeric constructs of the stromelysin promoter linked to the bacterial gene chloramphenicol acetyltransferase (CAT), we show that the elements required for the tumor promoter phorbol myristate acetate (PMA), epidermal growth factor (EGF), and interleukin 1 beta (IL-1 beta) induction are contained on a 307 base pair fragment which includes approximately 270 base pairs (bp) of 5'-flanking DNA. The cloning of the human stromelysin and stromelysin 2 genes, the documentation of their differential expression, and the identification of transcriptional regulatory regions in the stromelysin gene will facilitate the study of metalloproteinase gene expression in normal processes and in diseases such as rheumatoid arthritis.
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PMID:Cloning of the genes for human stromelysin and stromelysin 2: differential expression in rheumatoid synovial fibroblasts. 260 16

Stromelysin-1, matrix metalloproteinase-3 (MMP-3), is an important endopeptidase selectively expressed by somatic cells in organ tissues. The renal tubulointerstitium, for example, comprises tubular epithelium and interstitial fibroblasts forming the principal mass of the kidney. We observed that mRNA encoding stromelysin-1 is detectable in murine renal fibroblasts, but not in proximal tubular epithelium. Transcripts measured by RNase protection assay in renal fibroblasts increase following exposure to phorbol ester, and thereafter, activated stromelysin-1 protein can be detected in culture media by Western blotting. A 6.4 Kb genomic clone containing the putative stromelysin-1 promoter was isolated and a relevant 2.1 Kb PstI restriction fragment including 2.1 Kb of the immediate 5'-flanking region was sequenced on both strands. Two transcriptional start sites were identified by primer extension; the major start site corresponded to a previously established position in the rat promoter, and a second undescribed minor transcriptional start site was located 16 bp upstream of the primary site. A HiNF-A chromatin-activating element at -106 bp was found in the early promoter region of pR336 and an active AP-1 site at -72 bp with an Ets/PEA-3 motif at -203 bp was suggested by transient transfection of luciferase minigenes into renal fibroblasts responsive to phorbol ester. This Ets element was identical to a site in the early promoter of the fibroblast-specific gene FSP1. A baseline enhancement in activity of pR336 in fibroblasts was further observed with the addition of 5' flanking sequence out to -1980 bp. This additional region of flanking sequence contains two modular regions: one of multiple PEA-3 elements between -684 bp and -1955 bp and a second region between -1929 bp and -1980 bps containing a second AP-1 site at -1929 bp, a MBF-1/ MEP-1 metal binding site, and a PPAR peroxisome proliferator element at -1950 bp. Our findings implicate a gene structure with expected activity in a mesenchymal phenotype. The PKC-dependent regulation of the stromelysin-1 gene supports the notion that it may be modulated during inflammation or tissue remodeling.
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PMID:Identification of promoter activity and differential expression of transcripts encoding the murine stromelysin-1 gene in renal cells. 921 54