Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Qing-Luo-Yin (QLY), a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, is a combination of the extracts of Sophora flavescens Ait., Phellodendron amurense Rupr., Sinomenium acutum Rehd. et Wils. and Dioscorea hypoglauca Palib. The suppressive effect of QLY on the development of angiogenesis was investigated in a rat model of collagen-induced arthritis (CIA). QLY (0.3 g/kg) was orally administered daily for 27 days. Neo-angiogenesis, pannus and cartilage damage, the expression of metalloproteinases (MMP)-3 messenger RNA (mRNA) and the level of the tissue inhibitor of matrix metalloproteinase (TIMP)-1 in the synovium were examined by histology, in situ hybridization and immunohistochemiscal assays, respectively. It was observed that the articular morphological alterations, the over-expression of MMP-3 mRNA and the reduced production of TIMP-1 in CIA rats were significantly ameliorated by QLY. QLY performed about as effectively as tripterygium glycosidorum tablets (0.1 g/kg) extracted from Tripterygium wilfordii Hook. f.. These results indicate that QLY exerts a suppressive effect on the angiogenesis of CIA rats, and suggest that the therapeutic effect of QLY could be due to restoring the balance of MMP-3 and TIMP-1 in rheumatoid synovium.
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PMID:Suppressive effects of a Chinese herbal medicine qing-luo-yin extract on the angiogenesis of collagen-induced arthritis in rats. 1469 74

Membrane type 1-matrix metalloproteinase (MT1-MMP) is a major mediator of collagen I degradation. In human samples, we show that prostate cancer cells in skeletal metastases consistently express abundant MT1-MMP protein. Because prostate cancer bone metastasis requires remodeling of the collagen-rich bone matrix, we investigated the role of cancer cell-derived MT1-MMP in an experimental model of tumor-bone interaction. MT1-MMP-deficient LNCaP human prostate cancer cells were stably transfected with human wild-type MT1-MMP (MT1wt). Furthermore, endogenous MT1-MMP was down-regulated by small interfering RNA in DU145 human prostate cancer cells. Intratibial tumor injection in severe combined immunodeficient mice was used to simulate intraosseous growth of metastatic tumors. LNCaP-MT1wt cells produced larger osseous tumors than Neo control cells and induced osteolysis, whereas DU145 MT1-MMP-silenced transfectants induced osteogenic changes. In vitro assays showed that MT1wt overexpression enhanced collagen I degradation, whereas MT1-MMP-silencing did the opposite, suggesting that tumor-derived MT1-MMP may contribute directly to bone remodeling. LNCaP-MT1wt-derived conditioned medium stimulated in vitro multinucleated osteoclast formation. This effect was inhibited by osteoprotegerin, a decoy receptor for receptor activator of nuclear factor kappaB ligand, and by 4-[4-(methanesulfonamido) phenoxy] phenylsulfonyl methylthiirane, an MT1-MMP inhibitor. Our findings are consistent with the hypothesis that prostate cancer-associated MT1-MMP plays a direct and/or indirect role in bone matrix degradation, thus favoring intraosseous tumor expansion.
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PMID:Prostate cancer-associated membrane type 1-matrix metalloproteinase: a pivotal role in bone response and intraosseous tumor growth. 1752 76

Angiotensin (Ang) II, via type 1 receptor activation, exerts a significant role in atherogenesis and collagen synthesis. To test the hypothesis that Ang II type 2 receptor (AT2R) upregulation delivered with adeno-associated virus type 2 (AAV/AT2R) would inhibit collagen synthesis in atherosclerotic arteries, LDLR knockout mice were injected with AAV/AT2R and fed 4% cholesterol diet for 18 weeks. LDLR knockout mice treated with saline or AAV/Neo exhibited extensive vessel wall collagen accumulation, which was reduced by about 50% with AT2R over-expression. AT2R upregulation completely blocked the alterations in the expression of procollagen-I, osteopontin, fibronectin, CD68, and matrix metalloproteinases (MMP-2 and MMP-9), as well as phosphorylation of p38 and p44/42 MAPKs. Activity of superoxide dismutase was reduced in the LDLR KO mice and it increased with AT2R upregulation. This study demonstrates that AT2R over-expression reduces enhanced collagen accumulation, MMP expression and activity in atherosclerotic regions via inhibition of pro-oxidant signals.
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PMID:Over-expression of angiotensin II type 2 receptor (agtr2) decreases collagen accumulation in atherosclerotic plaque. 1803 70