Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation. This involves cellular migration across various structures associated with the blood-brain barrier: the vascular endothelium, the glia limitans, and the perivascular space between them. Leukocytes accumulate spontaneously in the perivascular space in brains of transgenic (Tg) mice that overexpress CCL2 under control of a CNS-specific promoter. The Tg mice show no clinical symptoms, even though leukocytes have crossed the endothelial basement membrane. Pertussis toxin (PTx) given i.p. induced encephalopathy and weight loss in Tg mice. We used flow cytometry, ultra-small superparamagnetic iron oxide-enhanced magnetic resonance imaging, and immunofluorescent staining to show that encephalopathy involved leukocyte migration across the glia limitans into the brain parenchyma, identifying this as the critical step in inducing clinical symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor of metalloproteinase-1, metalloproteinase disintegrins-12, MMP-8, and -10 in brains of Tg mice. Levels of the microglial-associated MP MMP-15 were not affected in control or PTx-treated Tg mice. PTx also up-regulated expression of proinflammatory cytokines IL-1beta and TNF-alpha mRNA in Tg CNS. Weight loss and parenchymal infiltration, but not perivascular accumulation, were significantly inhibited by the broad-spectrum MP inhibitor BB-94/Batimastat. Our finding that MPs mediate PTx-induced parenchymal infiltration to the chemokine-overexpressing CNS has relevance for the pathogenesis of human diseases involving CNS inflammation, such as multiple sclerosis.
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PMID:Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system. 1708 42

Matrix metalloproteinase (MMP) comprises a family of zinc-dependent endopeptidases that degrade various components of the extracellular matrix (ECM) and basement membrane. MMPs are involved in solid and hematological malignancy through modification of cell growth, activation of cancer cells and modulation of immune functions. Several polymorphisms of different MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A) & MMP-9 (-1562 C/T) and their expression levels have been well documented in different types of solid cancer. These polymorphic variations were found to be associated with angiogenesis, cancer progression, invasion and metastasis. There is paucity of data available in the field of hematological malignancies. Hence the field of matrix biology of hematological malignancies is an area of active exploration. A number of MMP inhibitors (MMPIs) have been developed for the cancer treatment. The most extensively studied classes of MMP inhibitors include Batimastat, Marismastat, Salimatat, Prinomastat and Tanomastat. However, their efficacy and action have not been confirmed and more data is required. The application of one or more selective targeted MMPIs in combination with conventional anti-leukemic treatment may represent a positive approach in combat against hematopoietic malignancies. Balance of MMPs and TIMPs is altered in different malignancies and biochemical pathways. These alternations will add another dimension in the matrix biology of both solid tumor and leukemia. MMP and TIMP singly and in combination are increasingly being recognized as an important player in basic cellular biology. Exploration and exploitation of MMP and TIMP balance in various malignant and nonmalignant lesions is going to be one of the most interesting facets of future use of this system for human health care.
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PMID:Matrix metalloproteinase and its drug targets therapy in solid and hematological malignancies: an overview. 2337 Apr 82

Mechanical stimulation is an essential factor for organisms to develop normally. In bladder development matrix metalloproteinases (MMPs) play an important role through structure remodeling and regulating the cell proliferation. In this study, we investigated the simulated physiological stretch induced proliferation of HBSMCs; MMPs/TIMPs expression in stretch and non-stretch groups. HBSMCs were exposed to cyclic stretch with defined parameters (5%, 10% and 15% elongation). The expression of MMPs and TIMPs in each parameter and non-stretch groups was examined at the transcriptional and translational levels respectively. 5-Ethynyl-2'-deoxyuridine (EdU) assay was used to assess cell proliferation. In the presence of the broad spectrum MMPs inhibitor (Batimastat), cells proliferation, MMPs and tissue inhibitors of metalloproteinases (TIMPs) expression were assessed again. Compared with non-stretch group, HBSMCs in stretch groups showed higher proliferation. The expression of MMP-1, 2, 3, 7 was up-regulated in stretch groups, and it remained at the same high level in 10% and 15% stretch groups. TIMP-1, 2 expression only increased under 15% stretch. Stretch resulted in elevated cell proliferation was abolished by Batimastat. In conclusion, the proliferation of HBSMCs induced by stretch was resulted from the stretch-induced MMPs expression and release.
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PMID:Simulated physiological stretch-induced proliferation of human bladder smooth muscle cells is regulated by MMPs. 2526 62


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