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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may be involved in tissue remodelling in the primate corpus luteum (CL). MMP/TIMP mRNA and protein patterns were examined using real-time PCR and immunohistochemistry in the early, mid-, mid-late, late and very late CL of rhesus monkeys. MMP-1 (interstitial collagenase) mRNA expression peaked (by >7-fold) in the early CL. MMP-9 (gelatinase B) mRNA expression was low in the early CL, but increased 41-fold by the very late stage. MMP-2 (gelatinase A) mRNA expression tended to increase in late CL. TIMP-1 mRNA was highly expressed in the CL, until declining 21-fold by the very late stage. TIMP-2 mRNA expression was high through the mid-luteal phase. MMP-1 protein was detected by immunocytochemistry in early steroidogenic cells. MMP-2 protein was prominent in late, but not early CL microvasculature. MMP-9 protein was noted in early CL and labelling increased in later stage steroidogenic cells. TIMP-1 and -2 proteins were detected in steroidogenic cells at all stages. Thus, MMPs and TIMPs are dynamically expressed in a cell-specific manner in the primate CL. Early expression of MMP-1 is suggestive of a role in tissue remodelling associated with luteinization, whereas MMP-2 and -9 may contribute to later stage luteolysis. TIMP expression may control MMP activity, until declining at luteolysis.
Mol Hum Reprod 2002 Sep
PMID:Dynamic expression of mRNAs and proteins for matrix metalloproteinases and their tissue inhibitors in the primate corpus luteum during the menstrual cycle. 1220 Apr 61

In this study we have attached cyclic targeting peptides by way of a poly-lysine spacer on the surface of an adenovirus using a transglutaminase enzymatic reaction to enhance transduction efficiency and to modify tissue tropism in vivo. Nuclear targeted lacZ- and TIMP-1-encoding adenoviruses were coupled to a peptide-motif (HWGF) that can bind to matrix metalloproteinase (MMP)-2 and MMP-9. Modified viruses were used to evaluate gene transfer efficiency, biodistribution, and the effect on neointima formation following balloon denudation injury. In vitro, both rabbit aortic smooth muscle cells and human endothelial hybridoma cells demonstrated significantly increased reporter gene expression with HWGF-modified adenoviruses (AdlacZ(HWGF)) compared with control (AdlacZ) or mismatch peptide-modified (AdlacZ(MM)) adenoviruses. However, in human hepatocellular Hep-G2 cells, both AdlacZ(HWGF) and AdlacZ(MM) produced significantly lower transgene expression compared with the respective control viruses. In vivo, local intravascular catheter-mediated gene transfer of a HWGF-targeted TIMP-1-encoding adenovirus (AdTIMP-1(HWGF)) significantly reduced intimal thickening in a rabbit aortic balloon denudation model (P < 0.05) compared with the control adenovirus. X-Gal staining and biodistribution analyses with TaqMan RT-PCR revealed that the cyclic peptides altered vector tropism and, in particular, reduced transduction of the liver. We found that the HWGF peptide modification increased transduction efficiency of the adenovirus-mediated gene transfer in smooth muscle cells and endothelial cells in in vitro and enhanced gene transfer to the arterial wall in vivo; that peptide modification of adenoviruses beneficially modulated tissue tropism in vivo; and that efficient TIMP-1 gene transfer reduced intimal thickening in an established restenosis model in rabbits.
Mol Ther 2002 Sep
PMID:Peptide-retargeted adenovirus encoding a tissue inhibitor of metalloproteinase-1 decreases restenosis after intravascular gene transfer. 1223 Nov 65

Extensive tissue remodeling occurs in the corpus luteum (CL) during both formation and luteolysis. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are believed to play pivotal roles in these processes. In the present study, to evaluate the potential roles of matrix degrading proteases in luteal development and regression, we examined gelatinases and TIMP-1, -2, -3 mRNA expressions, as well as gelatinase activity in rat CL during pregnancy and postpartum using Northern blot, in situ hybridization, and gelatin zymography, respectively. The results showed that MMP-2 mRNA was only expressed at the early stages of pregnancy; TIMP-2 mRNA was highly expressed at the early and late pregnancy and day 1 postpartum, but could not be detected during the mid-phase of pregnancy; TIMP-3 mRNA expression was abundant during early pregnancy and peaked at day 7, but was absent from other time points examined. MMP-9 and TIMP-1 mRNAs in rat CL were below detectable level in the current study. Furthermore, the active MMP-2 was only present during the early stages of pregnancy, and no MMP-9 activity was observed in the zymogram. Taken together, our results suggest that MMP-2 and TIMP-3 may have functional roles in rat luteal formation, while TIMP-2 may be implicated in both formation and regression of the pregnant CL.
Mol Reprod Dev 2002 Nov
PMID:Expression of gelatinases and their tissue inhibitors in rat corpus luteum during pregnancy and postpartum. 1223 42

Matrix-degrading metalloproteinases may play a role in the pathophysiology of bronchopulmonary dysplasia (BDP). We, therefore, evaluated correlations between gelatinase activities [metalloproteinase (MMP)-2 and MMP-9] or tissue inhibitor of metalloproteinase (TIMP)-1 levels present in the airways during the initial phase of hyaline membrane disease and the onset of BPD. Tracheal aspirates were obtained within 6 h of birth (day 0) from 64 intubated neonates with a gestational age < or =30 wk. Forty-five neonates were resampled on day 3 or 5. Total MMP-2 level measured by zymography fell with time, whereas total MMP-9 level and TIMP-1 levels, assayed by ELISA, increased; the MMP-9 increase correlated with the increase in airway inflammatory cell numbers. Among the parameters measured on day 0, 3, or 5, lower total MMP-2 level, lower birth weight, and higher fraction of inspired oxygen on day 0 were significantly and independently associated with the development of BPD. In conclusion, MMP-9 level and TIMP-1 levels increased after birth but are not linked to BPD outcome. In contrast, low MMP-2 level at birth is strongly associated with the development of BPD.
Am J Physiol Lung Cell Mol Physiol 2002 Nov
PMID:Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia. 1237 62

The upregulation of TIMP-1 following an excitotoxic injury has recently been hypothesized to be part of a general neuronal response that mediates long-lasting changes involved in tissue reorganization and possibly neuroprotection. In this study we have shown for the first time that within hours of applying TIMP-1 in recombinant form or by adenovirus-mediated gene transfer, neurons are highly protected against excitotoxic injury. Neither TIMP-3 nor a nonsecretable form of TIMP-1 protected neurons. TIMP-1 conferred highly significant protection to hippocampal cells exposed to a wide range of glutamic acid concentrations in both dissociated and organotypic hippocampal cultures. TIMP-1 did not prevent apoptotic cell death or death mediated by chemical ischemia. The observed neuroprotection may be explained by a decrease in calcium influx into neurons following stimulation with glutamate. These findings have a fundamental implication for our understanding of the physiological role of secreted TIMP-1 in the central nervous system.
Mol Cell Neurosci 2003 Jan
PMID:Tissue inhibitor of metalloproteinase 1 inhibits excitotoxic cell death in neurons. 1259 42

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate proteolysis of the extracellular matrix and other extracellular proteins, including growth factors and their receptors. The aberrant expression of these genes is common in most cancers. We profiled the RNA levels of every human MMP and TIMP in a variety of cell types (fibroblast, endothelial, hematopoietic, carcinoma, melanoma, and glioma) using quantitative PCR, with the aim of identifying novel expression patterns. Almost all members of the membrane-type (MT-) MMP and TIMP families were elevated in glioma lines compared to carcinomas. In clinical glioma specimens, there were positive correlations between glioma grade and RNA levels of MT-1, MT-2, and MT-6 MMP, TIMP-1 and TIMP-2, and for several growth factors and receptors. These findings suggest that advanced malignant gliomas have elevated levels of membrane-associated MMPs and TIMPs, which may potentially regulate vascularization and invasion. Concurrent elevation of signaling molecules suggests potential bidirectional relationships that enhance tumor aggressiveness.
Mol Cancer Res 2003 Mar
PMID:Elevated membrane-type matrix metalloproteinases in gliomas revealed by profiling proteases and inhibitors in human cancer cells. 1265 7

Matrix metalloproteinase (MMP)-9 secreted by activated polymorphonuclear neutrophils (PMN) may play roles in mediating lung injury by degrading extracellular matrix proteins. However, the mechanisms by which MMP-9 retains activity in the presence of tissue inhibitors of metalloproteinases (TIMPs) are not known. We show that MMP-9 is also expressed on the cell surface of PMN, and proinflammatory mediators induce up to 10-fold increases in cell surface expression of MMP-9. Stimulated human PMN express active forms of cell surface MMP, which cleave the MMP substrate, McaPLGLDpaAR. Loss-of-function studies employing PMN from mice genetically deficient in MMP-9 (MMP-9-/-) demonstrate that membrane-bound MMP-9 contributes substantially to MMP-mediated surface-bound cleavage of McaPLGLDpaAR (approximately 50%) and gelatin (approximately 70%) by stimulated PMN. Like soluble MMP-9, membrane-bound MMP-9 cleaves McaPLGLDpaAR (Kcat/KM = 82,000 M-1s-1), gelatin, type IV collagen, elastin, and alpha1-proteinase inhibitor. However, in contrast to soluble MMP-9, membrane-bound MMP-9 is substantially resistant to inhibition by TIMPs. The IC50 for inhibition of membrane-bound MMP-9 by TIMP-1 and TIMP-2 are approximately 21-fold and approximately 68-fold higher, respectively, than those for inhibition of soluble MMP-9. The binding of MMP-9 to the plasma membrane of PMN enables it to evade inhibition by TIMPs, and thereby may alter the pericellular proteolytic balance in favor of extracellular matrix degradation. Membrane-bound MMP-9 on PMN may play pathogenetic roles in inflammatory lung diseases.
Am J Respir Cell Mol Biol 2003 Sep
PMID:Inducible expression of tissue inhibitor of metalloproteinases-resistant matrix metalloproteinase-9 on the cell surface of neutrophils. 1266 32

Larvae of the Chilean-Peruvian scallop Argopecten purpuratus were fed a Dunaliella tertiolecta diet (Dun-diet) supplemented with lipid emulsions, rich in 20:5n-3 (EmEPA), 22:6n-3 (EmDHA) or in saturated fatty acids (EmCOCO). A mixed algal diet of Isochrysis galbana (T-iso) and Chaetoceros neogracile served as a positive control (St-diet). Lipid supplementation to the Dun-diet improved the larval growth and increased the percentage of eyed larvae significantly, compared to the non-supplemented Dun-diet because of the extra energy supplied and not because of its fatty acid composition. No significant differences were observed between supplementation with EmEPA, EmDHA or EmCOCO. A mixture of 20% EmEPA+20% EmDHA (40% EmHUFA) was more efficient in raising the total lipid content in larvae than 40% EmCOCO. Both emulsions increased the triacylglycerol content in larvae compared to the non-supplemented Dun-diet. The best result, however, was obtained with the St-diet, probably because of a more suitable 18:2n-6/18:3n-3 ratio and a higher level of arachidonic acid. A positive relationship between the 18:2n-6/18:3n-3 ratio and the larval performance was found. No significant difference was observed in post-settlement larval size or percentage of metamorphosed larvae between the St-diet and the St-diet supplemented with 20% EmHUFA or 20% EmCOCO. The metamorphosed larvae had a constant DHA/EPA ratio of 3.7, independent from the diet, which suggested a metabolic control of the two fatty acids and a species-dependency of the ratio.
Comp Biochem Physiol B Biochem Mol Biol 2003 Apr
PMID:Energy vs. essential fatty acids: what do scallop larvae (Argopecten purpuratus) need most? 1267 Jul 87

Serum lipid responses to dietary modification are partly determined by genetic factors. The objective of the present study was to investigate the influence of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene on serum lipid and lipoprotein responses to n-3 fatty acid supplementation. A total of 76 men and 74 women (age 49+/-8 years, body mass index 26.5+/-3.0 kg/m(2)) participated in a controlled multi-center study. Subjects were randomly assigned to consume either fish oil supplements (3.6g n-3 fatty acids/day containing 2.4 g of EPA and DHA) or placebo capsules containing olive oil for 3 months. At baseline, the Pro12Ala polymorphism was not associated with serum total and lipoprotein lipid concentrations or lipoprotein lipase activity in the fasting state. After the 3-month study period, carriers of the Ala12 allele presented a greater decrease in serum triacylglycerol concentration in response to n-3 fatty acid supplementation than did subjects with the Pro12Pro genotype when the total dietary fat intake was below 37 E% (p=0.003) or the intake of saturated fatty acids was below 10 E% (p=0.006). Changes in serum total cholesterol, serum LDL cholesterol and HDL cholesterol concentrations were similar among the genotypes in the n-3 fatty acid supplementation group and in the placebo group. In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene may modify the inter-individual variability in serum triacylglycerol response to n-3 fatty acid supplementation.
Mol Genet Metab 2003 May
PMID:Impact of the Pro12Ala polymorphism of the PPAR-gamma2 gene on serum triacylglycerol response to n-3 fatty acid supplementation. 1276 46

Mechanisms underlying structural reorganization of the uterine artery in pregnancy remain largely unknown. Matrix metalloproteinases (MMPs) which are involved in degradation of vascular wall matrix are likely to play a key role. In this investigation of rat uterine artery, key MMPs and the specific tissue inhibitors of MMPs (TIMPs) together with three housekeeping genes were studied before, during and after pregnancy, using real time PCR. Data were analysed by partial least squares analysis as well as by conventional univariate methods. Each gene studied [MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, MMP-13, membrane-type 1 (MT1)-MMP, TIMP-1, TIMP-2, GAPDH, cyclophilin and beta-actin] increased in late pregnancy (day 21). MMP-2, MT1MMP, MMP-3 and TIMP-1 transcripts were also elevated at day 7. TIMP-1 and MMP-3 mRNA expression returned to virgin control values in the post-partum, whereas others remained elevated or increased further (MMP-9, MMP-13). Gelatin zymography showed maximum elevation of MMP-2 at day 21. A novel 43-45 kDa gelatinolytic doublet was observed which increased in density with gestation and may represent an active MMP-2 fragment. Together, these data strongly suggest that MMPs and TIMPs are likely to play an important role in remodelling uterine arteries in rat pregnancy and may represent means by which vasodilatation is maintained in later pregnancy. Continued elevated levels of some MMPs post-partum may contribute to vessel regression and return to a non-pregnant physiological state.
Mol Hum Reprod 2003 Jun
PMID:Gestational profile of matrix metalloproteinases in rat uterine artery. 1277 Dec 36


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