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)

Epidermal growth factor (EGF) is a ubiquitous fibroblast mitogen which also stimulates the synthesis of the extracellular matrix degrading metalloproteinases, collagenase, and stromelysin. Using primary cultures of human skin fibroblast, we show that these metalloproteinase mRNAs are coordinately up-regulated by EGF; and that dexamethasone, a potent inhibitor of collagenase and stromelysin synthesis, coordinately down-regulates these EGF-induced mRNAs. Nuclear run-on assays showed that EGF increased transcription of collagenase and stromelysin approximately 2-fold over the untreated control, while repression by dexamethasone was difficult to detect. However, steady state mRNA levels were induced approximately 10-fold by EGF and co-treatment with dexamethasone decreased them to below control levels, suggesting modulation of mRNA stability. Thus, we measured the half-life of these mRNAs using "pulse-chase" methodology. Typically, the half-life of EGF-induced collagenase and stromelysin mRNAs was approximately 30 h, and co-treatment with dexamethasone decreased the half-life of these mRNAs by 30-50%. Additionally, we found that the transcription inhibitor DRB stabilized EGF-induced metalloproteinase mRNAs, suggesting an mRNA degradation pathway which requires transcription. Thus our data demonstrate that collagenase and stromelysin are coordinately regulated by EGF and by dexamethasone, primarily at the level of metalloproteinase mRNA stability.
 ...
PMID:Post-transcriptional regulation of collagenase and stromelysin gene expression by epidermal growth factor and dexamethasone in cultured human fibroblasts. 146 71

The in vitro effects on human articular chondrocytes were evaluated for a series of N-benzo[d]isothiazol-3-yl-amidines, bearing as pharmacophoric moiety the nonacidic isosteric nitrogen analogue of the carboxylic group. The aim was to verify their effectiveness in articular diseases, such as arthritis. Human chondrocytes were treated with IL-1beta in the presence of a series of N-benzo[d]isothiazol-3-yl-amidines at a concentration of 100 microg/mL. After 120 h, the amount of glycosaminoglycans (GAGs), the production of nitric oxide (NO) and the inhibition of metalloproteinases (MMP-3) and prostaglandin (PGE2) were measured. Nitrite production induced by inflammatory IL-1beta on cultured chondrocytes was inhibited by the N-benzo[d]isothiazol-3-yl-amidines tested, in particular by N-benzo[d]isothiazol-3-yl-benzamidine, which was the most active. Concerning the effects on GAGs, all the tested benzisothiazolylamidines, and in particular N-benzo[d]isothiazol-3-yl-acetamidine, prevented the depletion of proteoglycan induced by IL-1beta. Inhibitory effects of the tested compounds on MMP-3 activity and on PGE2 production were also observed.
 ...
PMID:Protective effects of benzisothiazolylamidines on IL-1 beta induced alterations in human articular chondrocyte metabolism. 1567 65