The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity

Murphy, Gillian; Houbrechts, Annick; Cockett, Mark I.; Williamson, Richard A.; O'Shea, Mark; Docherty, Andrew

doi:10.1021/bi00247a001

Cited by 311 publications

(229 citation statements)

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“…TIMP-1 is a well-characterized specific inhibitor of MMPs. It interacts noncovalently with active metalloproteinases, including MMP-2 and MMP-9, and also binds to the proform of MMP-9, thus regulating its activation (26,36). It is secreted by a wide variety of cell types, including lung epithelial cells, fibroblasts, alveolar macrophages, and neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…We thus studied premature infants with hyaline membrane disease to determine whether the profile of gelatinase activities at birth was associated with the subsequent risk of BPD and to examine the possible link between the early postnatal time course of gelatinase activities and clinical outcome. We also tested airway secretions for tissue inhibitor of metalloproteinases (TIMP)-1, a key specific inhibitor of MMPs that forms tight complexes with activated MMP-2 and MMP-9 (26,36).…”

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confidence: 99%

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Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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2002.-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 Յ30 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. metalloproteinase; lung development; newborn; extracellular matrix PREMATURE NEONATES WITH HYALINE membrane disease are at risk of developing bronchopulmonary dysplasia (BPD), as a sequel of both the disease and its treatment. The pathogenesis is unclear, but BPD is thought to result from damage to an immature lung. Mechanical ventilation, oxygen therapy, and airway inflammatory responses have all been implicated in the development of BPD (19). These insults appear to interfere with normal lung maturation, which is incomplete at birth. In particular, they appear to alter alveolar formation, on the basis of morphometric studies of severe BPD (3, 24). Alveolar formation is characterized by the multiplication of alveolar septa and the thinning of interalveolar walls, both of which require intense remodeling of the pulmonary extracellular matrix (4). Changes in matrix turnover have been experimentally linked to abnormal alveolar formation (20). The proteinase-antiproteinase balance in the lung is a key factor in harmonious matrix turnover. In particular, matrix metalloproteinases (MMPs), which can synergistically digest the major macromolecules of connective tissue matrices, have been implicated in physiological regulation of lung growth. The MMP gelatinase A (MMP-2) has been shown to play a role in the major collagen turnover that occurs during early postnatal rat lung growth (1, 2). We postulated that MMP-2 might also participate in human lung development and that inadequate MMP-2 levels in premature lungs exposed to insults could contribute to impaired lung growth and thus to BPD. We also postulated that MMPs may be secreted in excess during the inflammatory response associated with hyaline membrane disease and may, therefore, lead to tissue degradation. Gelatinase B (MMP-9) is the main MMP released by inflammatory cells such as neutrophils and alveolar macroph...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Second strand synthesis were harvested, clarified by centrifugation, and subjected to collagenwas performed with Escherichia coli T 4 DNA polymerase (Promega, ase and TIMP-1 activity assays as previously described. 39,40 The idenMadison, WI).…”

Section: Methodsmentioning

confidence: 99%

Tissue Inhibitor of Metalloproteinase–1 Messenger Rna Expression Is Enhanced Relative to Interstitial Collagenase Messenger Rna in Experimental Liver Injury and Fibrosis

et al. 1996

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In liver fibrosis and cirrhosis there is a change in both the Liver fibrosis results from a relative imbalance beamount and relative composition of the hepatic extracellular tween synthesis and degradation of matrix proteins. We matrix. 1 Current evidence suggests that hepatic stellate cells have previously described release of the potent collagen-(lipocytes, fat-storing or Ito cells) are central to this process ase inhibitor, tissue inhibitor of metalloproteinase-1 both as the major source of fibrillar and nonfibrillar matrix (TIMP-1), by culture-activated human hepatic stellate proteins and matrix degrading metalloproteinases. 1-11 cells (HSCs). In this study, we have investigated the relaWe have previously shown that cultured hepatic stellate tive expression of TIMP-1 and interstitial collagenase in cells (HSCs) activated to a myofibroblastic phenotype express culture-activated rat HSCs and rat models of liver injury gelatinase A (72-kd type IV collagenase/gelatinase) 12,13 and and fibrosis. The complementary DNA (cDNA) for rat there is evidence to suggest that they also secrete stromely-TIMP-1 was obtained by homology polymerase chain reaction (PCR) and sequenced. By Northern analysis using sin. 14 A further metalloproteinase, interstitial collagenase, this probe, TIMP-1 messenger RNA (mRNA) expression expressed by mesenchymal and other cell types has degradawas up-regulated with HSC activation by culture on tive activity against native collagen types I and III, 15,16 explastic as defined by cellular expression of procollagen-pression of which could potentially initiate remodelling of 1. Interstitial collagenase mRNA was expressed in early fibrotic liver. culture (õ4 days) but became undetectable in more actiInterstitial collagenase expression in liver has been varivated cells (7-21 days). By activity assay of serum-free ously ascribed to parenchymal and sinusoidal liver cells, incell-conditioned media, TIMP-1 was found to be released cluding Kupffer cells 17,18 and hepatocytes. 19,20 There is also in increasing concentrations with duration of culture on some evidence to indicate that HSCs are a cellular source of plastic. Expression of TIMP-1, interstitial collagenase, interstitial collagenase in liver; studies on a passaged celland procollagen-1 mRNAs were studied in rat models of line derived by outgrowth from human liver (of possible HSC biliary and parenchymal injury (bile duct ligation and origin) showed that interstitial collagenase is expressed conCCl 4 administration) by ribonuclease protection assay. stitutively and is up-regulated in response to interleukin-TIMP-1 mRNA expression was increased at 6, 24 hours, 1 and tumor necrosis factor a. 21 Li et al. have also shown and 3 days after bile duct ligation and was also shown collagenase activity in cultured rat HSCs which was into rise in acute CCl 4 liver injury and remain elevated as creased in response to polyunsaturated lecithin. 22 the liver became fibrotic. TIMP-1 expression precededIn studies undertaken to measure interstitial collagenase proc...

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“…Expression and Purification of Full-length MMP-19 -Human MMP-19 was purified from culture medium conditioned by NS0 mouse myeloma cells that had been transfected with MMP-19 cDNA, essentially as described previously (10). The expression vector, transfection method, and culture conditions were as described previously (11,12).…”

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confidence: 99%

“…Expression and Purification of Recombinant TIMPs-Recombinant forms of human TIMP-1, -2, and -3 were generated as described previously (11)(12)(13). TIMP-4 was expressed and purified from bacterial inclusion bodies, essentially as reported for TIMP-2 (14).…”

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confidence: 99%

Biochemical Characterization of the Catalytic Domain of Human Matrix Metalloproteinase 19

Stracke¹,

Hutton²,

Stewart³

et al. 2000

Journal of Biological Chemistry

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128

107

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We have recently cloned MMP-19, a novel matrix metalloproteinase, which, due to unique structural features, was proposed to represent the first member of a new MMP subfamily (Pendá s, A. M., Knä uper, V., Puente, X. S., Llano, E., Mattei, M. G., Apte, S., Murphy, G., and Ló pez-Otin, C. -Pro-Leu-Gly-Dpa-Ala-Arg-NH 2 and, with higher efficiency, the stromelysin substrate McaPro-Leu-Ala-Nva-Dpa-Ala-Arg-NH 2 . Kinetic analysis of the interactions of the catalytic domain of MMP-19 with the natural MMP inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), showed strong inhibition using TIMP-2, TIMP-3, and TIMP-4, while TIMP-1 was less efficient. We also demonstrated that synthetic hydroxamic acid-based compounds efficiently inhibited the enzyme. The catalytic domain of MMP-19 was able to hydrolyze the basement membrane components type IV collagen, laminin, and nidogen, as well as the large tenascin-C isoform, fibronectin, and type I gelatin in vitro, suggesting that MMP-19 is a potent proteinase capable of hydrolyzing a broad range of extracellular matrix components. Neither the catalytic domain nor the fulllength MMP-19 was able to degrade triple-helical collagen. Finally, and in contrast to studies with other MMPs, MMP-19 catalytic domain was not able to activate any of the latent MMPs tested in vitro.

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The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity

Cited by 311 publications

References 28 publications

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Tissue Inhibitor of Metalloproteinase–1 Messenger Rna Expression Is Enhanced Relative to Interstitial Collagenase Messenger Rna in Experimental Liver Injury and Fibrosis

Biochemical Characterization of the Catalytic Domain of Human Matrix Metalloproteinase 19

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