Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Matrix Metalloproteinases”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed2004

Anti-neovascular therapy by liposomal drug targeted to membrane type-1 matrix metalloproteinase.

Because membrane type-1 matrix metalloproteinase (MT1-MMP) is expressed specifically on the angiogenic endothelium as well as tumor cells, an agent possessing the ability to bind to this molecule might be useful as a tool for active targeting of tumor angiogenic vessels. Based on the sequences of peptide substrates of MT1-MMP, which had been determined by using a phage-displayed peptide library, we examined the binding ability of peptide-modified liposomes for endothelial cells and targeting ability for tumor tissues by positron emission tomography (PET). Liposomes modified with stearoyl-Gly-Pro-Leu-Pro-Leu-Arg (GPLPLR-Lip) showed high binding ability to human umbilical vein endothelial cells and accumulated in the tumor about 4-fold more than did the unmodified liposomes. Because we reported previously that liposomalized 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (DPP-CNDAC), a hydrophobized derivative of the novel antitumor nucleoside CNDAC, strongly suppressed tumor growth when delivered in liposomes modified with another angiogenic homing peptide, we examined the antitumor activity of DPP-CNDAC entrapped in GPLPLR-Lip. DPP-CNDAC/GPLPLR-Lip showed significant tumor growth suppression compared to DPP-CNDAC/unmodified liposomes. These results suggest that DPP-CNDAC-liposomes modified with MT1-MMP-targeted peptide are useful for cancer anti-neovascular therapy (ANET), namely, tumor growth suppression by damage to angiogenic endothelial cells.

Angiogenesis Inhibitors↗
PubMed2001

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human fetal testis and ovary.

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are major regulators of tissue remodelling of the extracellular matrix (ECM) and may also be involved in the control of growth factor availability. We have investigated their production and localization in the developing human gonad during mid-gestation using zymographic techniques and immunohistochemistry. The secretion of MMP-2, MMP-9 and all four TIMP was demonstrated from both testis and ovary, with the predominant gelatinase produced by both being MMP-2. In the testis, MMP-1, MMP-2, MMP-9 and all TIMP family members were localized to the interstitium and to varying degrees within the tubules. MMP-9 and TIMP-4 were abundant in both Sertoli cells and gonocytes and MMP-1 and TIMP-1 were localized in particular to Sertoli cells. In the ovary, all TIMP and MMP-1, MMP-2 and MMP-9 were localized to the oogonium/oocyte cytoplasm with varying intensities and MMP-1, TIMP-2 and TIMP-3 were also detected in the ovarian stroma. This study demonstrates that MMP-1, MMP-2, MMP-9 and all TIMP family members are secreted by the developing ovary and testis and are localized to specific cell and tissue sites. MMP and TIMP are likely to play a role in ECM remodelling during gonadal development and also in the cell and matrix interactions that control a range of cellular functions.

Culture Techniques↗
PubMed1996

Metastatic colorectal cancer cells induce matrix metalloproteinase release by human monocytes.

Matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) facilitate tumor invasion and metastasis via basement membrane degradation. In colorectal cancer (CRC) specimens, MMP production is largely stromal in origin, implicating monocytes (M phi s) and fibroblasts. We hypothesize that CRC cells induce stromal cell MMP production. This study examines the differential effect of metastatic and non-metastatic CRC cells on M phi MMP production. The human M phi line THP-1 was co-cultured with either a non-metastatic human CRC cell line (SW620-P) or a metastatic clone (SW620-S5) established by serial cecal transplantation of SW620-P in nude mice. Conditioned medium MMP activity and cellular MMP mRNA expression were assessed by gelatinase zymography and Northern blot analysis, respectively. Neither CRC line released MMP-2 or MMP-9. Isolated THP-1 M phi s produced basal levels of both MMP-2 and MMP-9. The level of MMP-9 activity was increased moderately by co-culture of M phi s with the metastatic SW620-S5 clone, but decreased by the non-metastatic SW620-P cells. MMP-2 activity was greatly augmented by co-culturing M phi s with SW620-S5 cells, but was not affected by SW620-P cells. The stimulatory effect of SW620-S5 cells on MMP-2 secretion was confirmed by Western blot analysis. Both isolated and co-cultured M phi s expressed MMP-2 mRNA while SW620-S5 cells under similar conditions did not, implicating M phi s as the source of increased MMP-2 activity. Since the induction of MMP-2 activity was not associated with a parallel increase in M phi MMP-2 mRNA, the modulation of M phi MMP-2 release appears to be post-transcriptionally regulated. Metastatic CRC cells are distinct from non-metastatic cells in their ability to induce M phi MMP release. This observation emphasizes the role of M phi-derived MMPs in facilitating CRC invasion and metastasis and suggests modulation of stromal cell MMP production by CRC cells in a paracrine fashion.

Animals↗
PubMed2003

Prolonged spinal loading induces matrix metalloproteinase-2 activation in intervertebral discs.

STUDY DESIGN: An established in vivo mouse model of compression-induced disc degeneration was used to investigate the effects of load on matrix catabolism. OBJECTIVES: To determine whether matrix metalloproteinase-2 expression in discs is modulated by mechanical load and to characterize the regulation of matrix metalloproteinase-2 activity. SUMMARY OF BACKGROUND DATA: We have previously shown that static compression of discs elicits changes in tissue architecture consistent with those seen with degeneration. Evidence in the literature demonstrates the existence of matrix metalloproteinases in both healthy and pathologic discs and suggests that mechanical load may influence matrix metalloproteinase expression and activity. METHODS: Static compression was applied to mouse coccygeal discs in vivo for 1, 4, or 7 days, with adjacent discs serving as sham control. An activity assay was used to measure concentrations of active and total matrix metalloproteinase-2, and changes in matrix metalloproteinase-2 gene expression relative to beta-actin were assessed by reverse transcriptase-polymerase chain reaction. RESULTS: Although no change was seen relative to sham after 1 day of load, the proportion of total matrix metalloproteinase-2 that was active increased after 4 days. This elevation was sustained through 7 days of compression, with no significant differences in total matrix metalloproteinase-2 concentrations among discs throughout the range of time points examined. Semiquantitative reverse transcriptase-polymerase chain reaction demonstrated no significant changes in matrix metalloproteinase-2 gene expression at 1 day or 4 days. CONCLUSIONS: In this model, regulation of matrix metalloproteinase-2 activity occurs primarily through enhanced molecular activation of the proenzyme rather than through elevated gene expression or translation. Our results suggest that matrix metalloproteinase-2 may have a role in load-induced changes in disc architecture.

Animals↗
PubMed1999

Decreased contraction of glycated collagen lattices coincides with impaired matrix metalloproteinase production.

Nonenzymatic glycation of extracellular matrix (ECM) proteins is increased in diabetes mellitus and aging and triggers cellular events leading to an imbalance in ECM homeostasis. We studied the influence of collagen glycation on matrix metalloproteinase production by dermal fibroblasts using the model of lattice cultures. Contraction of glycated collagen lattices was strongly reduced when compared to controls. Meanwhile, fibroblasts synthesized lower amounts of interstitial collagenase (MMP-1). Gelatinase A (MMP-2) production was not modified, but its activation was strongly inhibited. These effects were independent from the intensity of lattice contraction and from any simultaneous modification of tissue inhibitors of metalloproteinase (TIMP-1 and 2) production. These results demonstrate that the impaired ability of fibroblasts to remodel and contract a glycated extracellular matrix coincides with a decrease in MMP production.

Adult↗
PubMed2004

Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers.

PURPOSE: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tumor invasion; several individual members of which have been implicated in tumor prognosis. These enzymes and their physiologic inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), act in a coordinated manner to form an integrated system. Therefore, to understand their role in tumor invasion, it is necessary to evaluate them collectively. EXPERIMENTAL DESIGN: In this study all of the major members of the matrix metalloproteinase (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MT1-MMP and MT2-MMP)/tissue inhibitor of matrix metalloproteinase (TIMP-1, TIMP-2, and TIMP-3) system have been investigated by immunohistochemistry in a series (n = 90) of stage III (Dukes' C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and proportion of immunoreactive cells was established for each MMP and TIMP. RESULTS: The MMP/TIMP profile defined by hierarchical cluster analysis of the immunohistochemical score identifies a distinct group of colorectal cancers with poor prognosis (log-rank test, 12.22, P = 0.0005). The median survival time of patients in this survival group was 18 months compared with a median survival of 49 months in the "good" survival group. Multivariate analysis showed that this profile was independently the most significant prognostic factor (P = 0.001). CONCLUSIONS: This study has identified that the MMP/TIMP profile is an independent indicator of poor prognosis in colorectal cancer.

Adenocarcinoma↗
PubMed1997

Plasminogen activator and matrix metalloproteinase production and extracellular matrix degradation by rat prostate cancer cells in vitro: correlation with metastatic behavior in vivo.

BACKGROUND: The plasminogen activation (PA) and metalloproteinase (MMP) system are involved in tumor cell migration and invasion. METHODS: The proteolytic activity of cell lines originating from the rat Dunning R-3327 prostate tumor was analyzed by measuring in vitro extracellular matrix degradation, enzyme activity, and mRNA levels of enzymes, inhibitors, and receptors, and compared with their known metastatic behavior in vivo. RESULTS: Only the highly metastatic sublines AT-3, MATLu, and MATLyLu showed a high extracellular matrix degradation mediated by urokinase-type plasminogen activator (u-PA). Relatively high levels of u-PA were present in the aggressive cell lines. u-PA receptor mRNA was produced in all cells, and all but AT-1 produced LDL-receptor-related-protein (LRP) mRNA. t-PA mRNA was only found in HIF and MATLu. In gelatin, zymography lysis was observed at 72 kD and 74-76 kD in MATLu and MATLyLu cells, respectively. MMP-2 mRNA was present in all cell lines except AT-1 and AT-2, and MMP-3 mRNA was present in AT-2, AT-3, and MATLu. CONCLUSIONS: These in vitro experiments show that in different rat prostate cancer sublines, proteolytic activity and u-PA-mediated extracellular matrix degradation correlate with their known metastatic behavior in vivo.

Analysis of Variance↗
PubMed2003

Effect of gamma-synuclein overexpression on matrix metalloproteinases in retinoblastoma Y79 cells.

gamma-Synuclein is a small cytoplasmic protein implicated in neurodegenerative diseases and cancer. However, the mechanism of its involvement in diseases is not clear. We studied the role of gamma-synuclein in the regulation of matrix metalloproteinases in retinoblastoma cell culture. Matrix metalloproteinases play important roles in the remodeling of extracellular matrix implicated in tumor progression and in the neurodegenerative diseases. Western blot and zymography data demonstrated a moderate elevation of matrix metalloproteinases-2 and significant upregulation of matrix metalloproteinases-9 in stable cell lines overexpressing gamma-synuclein. No effect of gamma-synuclein overexpression on matrix metalloproteinases-1 level or activity was found. Chloramphenicol-acetyltransferase assay demonstrated that overexpression of gamma-synuclein increases the efficiency of the matrix metalloproteinases-9 promoter. This increment of promoter activity may be mediated by the AP-1 binding site(s), since point mutations in one of these sites (Pr18 or Pr19) and elimination of the distal AP-1 site (Pr14) reduced the increment of promoter activity.

Chloramphenicol O-Acetyltransferase↗
PubMed2003

Increased matrix metalloproteinase activity after canine cardiopulmonary bypass is suppressed by a nitric oxide scavenger.

OBJECTIVES: We tested whether nitric oxide scavenging with a ruthenium-based compound (AMD6221) would improve hemodynamics and alter nitric oxide synthase and matrix metalloproteinase activities in a canine model of cardiopulmonary bypass. METHODS: Dogs were randomized to either cardiopulmonary bypass (n = 12) or control (n = 12) groups. They were further randomized to receive a continuous infusion of AMD6221 or placebo. Cardiopulmonary bypass was maintained for 90 minutes, and then, 4 hours later, dogs were killed. Cardiac, lung, and brain sections were snap frozen in liquid nitrogen for determination of nitric oxide synthase, matrix metalloproteinase 2, and matrix metalloproteinase 9 activities. RESULTS: After cardiopulmonary bypass, 3 of 6 placebo-treated (cardiopulmonary bypass-placebo) and 0 of 6 AMD6221-treated (cardiopulmonary bypass-6221) animals required phenylephrine infusion to maintain a predetermined blood pressure (P <.05). Total fluid administration was lower in the cardiopulmonary bypass-6221 group compared with that in the cardiopulmonary bypass-placebo group (983 +/- 134 vs 1617 +/- 254 mL, respectively; P <.005). After cardiopulmonary bypass, matrix metalloproteinase 2 and matrix metalloproteinase 9 activities in the lung, left ventricle, and left atrium were decreased in the cardiopulmonary bypass-6221 group compared with that in the cardiopulmonary bypass-placebo group (P <.05). Ca(2+)-independent nitric oxide synthase activity and matrix metalloproteinase 2 activity in the brain were also lower (P <.05) in the cardiopulmonary bypass-SCV group. Finally, neutrophil expression of CD18, an adhesion complex, was lower at 4 hours after cardiopulmonary bypass in the cardiopulmonary bypass-6221 group compared with that in the cardiopulmonary bypass-placebo group (38 +/- 27 vs 81 +/- 11; P <.05). CONCLUSIONS: We found that (1) infusion of an nitric oxide scavenger, AMD6221, was associated with improved predefined hemodynamics; (2) cardiopulmonary bypass increased activities of Ca(2+)-independent nitric oxide synthase and matrix metalloproteinases in multiple organs; and (3) AMD6221 could ameliorate the increased generation of nitric oxide and increased matrix metalloproteinase activities.

Animals↗
PubMed2004

Prognostic significance of stromelysin-3 and tissue inhibitor of matrix metalloproteinase-2 in esophageal cancer.

OBJECTIVE: Stromelysins (matrix metalloproteinases: MMP-10 or ST-2 and MMP-11 or ST-3) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) have been shown to be associated with human tumor progression, invasion and metastasis. The aim of the present study was to determine the prognostic significance of these proteins in esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical analysis was carried out in 65 surgically resected ESCCs and 49 distant histologically normal esophageal tissues and 16 cases of dysplasias. Statistical analyses were performed to determine the associations between the protein expression and clinicopathological parameters and survival of esophageal cancer patients. RESULTS: Expression of ST-2, ST-3, TIMP-1 and TIMP-2 was observed in 43/65 (66%), 51/65 (78%), 43/65 (66%) and 47/65 (72%) ESCC cases, respectively. Univariate analysis showed that TIMP-2 expression was associated with tumor site (OR = 2.63, p = 0.017). TIMP-1+/TIMP-2+ phenotype was inversely correlated with nodal invasiveness of the tumor (OR = 0.4, p = 0.04). Interestingly, p53 expression was associated with increased levels of ST-3 (OR = 0.11, p = 0.02) and TIMP-1 (OR = 3.2, p = 0.007) suggesting possible involvement of p53 in the regulation of these proteins. An increased expression of ST-2, ST-3, TIMP-1 and TIMP-2 was observed in 11/16 (69%), 7/17 (44%), 11/16 (69%) and 8/16 (50%) dysplasias also suggesting that these alterations are early events in esophageal tumorigenesis. All the ESCC patients were followed up postesophagectomy for a maximum period of 59 months (mean disease-free survival = 12 months). Kaplan-Meier survival analysis showed that patients with ST-3-positive and TIMP-2-negative carcinoma had a significantly shorter disease-free survival (median disease-free survival time of 4 months) as compared to patients in the other groups (median disease-free survival time of 20 months; p = 0.0016). To our knowledge this is the first report showing that ST-3+/TIMP-2- phenotype remained of significant predictive value for disease-free survival (p = 0.0007) in multivariate analysis including a conventional clinicopathological factor, tumor stage (p = 0.051). CONCLUSION: Our results suggest that ST-3+/TIMP-2- phenotype is an adverse prognosticator in esophageal cancer patients.

Adult↗
PubMed2005

Expression of matrix metalloproteinase-3 in the rat cervix during pregnancy and in response to prostaglandin E2.

OBJECTIVE: The purpose of this study was to evaluate the expression of matrix metalloproteinase-3 in the cervix during normal pregnancy and in response to prostaglandin E2 administration to determine how matrix metalloproteinase-3 expression correlates with changes in cervical tensile strength. STUDY DESIGN: We assessed cervical tensile strength at different time points in the rat gestation and after the administration of prostaglandin E2. Tensile strength was determined by the cervical creep method. Both active and latent forms of matrix metalloproteinase-3 protein were assayed by immunoblotting and densitometry. Matrix metalloproteinase-3 messenger RNA expression was determined with a real-time reverse transcriptase-polymerase chain reaction technique. RESULTS: Cervical tensile strength decreased through the second half of gestation, reaching a nadir by day 21, at 24 to 48 hours before parturition. Prostaglandin E2 that was administered on day 20 of gestation decreased cervical tensile strength in animals that were pretreated with indomethacin. Prostaglandin E2 treatment before day 20 of gestation produced no change in cervical tensile strength. Matrix metalloproteinase-3 messenger RNA and active protein expression paralleled the changes in cervical tensile strength during normal gestation. No change in total matrix metalloproteinase-3 protein expression was detected after prostaglandin E2 treatment. CONCLUSION: Matrix metalloproteinase-3 expression parallels changes in cervical tensile strength through pregnancy. Prostaglandin E2 induces the activation of matrix metalloproteinase-3 but does not affect matrix metalloproteinase-3 protein expression, which suggests that matrix metalloproteinase-3 gene transcription is not regulated by prostaglandin E2 but that rather there is another mechanism by which change is induced.

Animals↗
PubMed2004

Matrix metalloproteinase-8 is expressed in human chorion during labor.

OBJECTIVE: The purpose of this study was to investigate the expression of matrix metalloproteinase-8 by human fetal membranes during labor. STUDY DESIGN: Fetal membranes were obtained from women who underwent normal labor or elective cesarean delivery at term. Matrix metalloproteinase-8 levels in fetal membranes were determined by enzyme-linked immunosorbent assay and Western blot; the expression of the matrix metalloproteinase-8 gene was detected by reverse transcription-polymerase chain reaction. Immunohistochemistry and in situ hybridization was performed to localize matrix metalloproteinase-8 protein and messenger RNA in intact membranes. RESULTS: Matrix metalloproteinase-8 protein levels were increased 5-fold in fetal membranes from labor compared with membranes that were obtained from cesarean delivery. Western blots confirmed the presence of matrix metalloproteinase-8 in protein extracts. Reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemistry demonstrated that matrix metalloproteinase-8 messenger RNA and protein were expressed almost exclusively in the chorion after labor. CONCLUSION: We conclude that matrix metalloproteinase-8 is produced primarily by chorionic cells in human fetal membranes and that the level of matrix metalloproteinase-8 protein and messenger RNA expression in fetal membranes increases during labor.

Blotting, Western↗
PubMed2002

Identification of matrix metalloproteinase-9 in amniotic fluid and amniochorion in spontaneous labor and after experimental intrauterine infection or interleukin-1 beta infusion in pregnant rhesus monkeys.

OBJECTIVE: The purpose of this study was to examine the roles of intrauterine infection, inflammation, and spontaneous labor on the expression of matrix metalloproteinase-9 in fetal membranes and amniotic fluid of late pregnant rhesus monkeys. STUDY DESIGN: Pregnant rhesus monkeys with timed gestations were chronically catheterized to allow serial sampling of amniotic fluid before and during experimentally induced intrauterine inflammation. Six animals received group B streptococci into the chorionic-decidual space, and 4 animals received intra-amniotic interleukin-1 beta infusions (10 microg). Three additional animals were serially sampled by amniocentesis through late pregnancy until spontaneous term labor. Amniotic fluid samples were examined by zymography for matrix metalloproteinase-9 and -2 and Western immunoblot for matrix metalloproteinase-9 and -2 and tissue inhibitors of metalloproteinase-1 and -2. Fetal membranes were obtained at cesarean delivery during labor (before rupture), formalin fixed, and embedded in paraffin for immunocytochemistry of matrix metalloproteinase-9 and in situ hybridization of matrix metalloproteinase-9 messenger RNA. Tissues from 2 additional animals were collected as age-matched non-labor controls. RESULTS: In amniotic fluid, the 92-kd latent matrix metalloproteinase-9 was detectable in late pregnancy and increased dramatically, followed by the appearance of the 83-kd active form before spontaneous term delivery. Amniotic fluid matrix metalloproteinase-2 levels (both latent and active forms) remained relatively constant throughout pregnancy and in labor. Both bacteria and interleukin-1 beta rapidly increased the signal of latent matrix metalloproteinase-9 without a consistent increase in the active form before the onset of labor. Chorionic-decidual inoculation of group B streptococci was followed by the expression of latent matrix metalloproteinase-9 before the appearance of group B streptococci in amniotic fluid or the onset of labor. Matrix metalloproteinase-2 increased to a new steady-state level or remained unchanged after group B streptococci inoculation or interleukin-1 beta infusion, respectively. Amniotic fluid tissue inhibitors of metalloproteinase-1 declined and tissue inhibitors of metalloproteinase-2 remained unchanged during early group B streptococci infection, after interleukin-1 beta infusion and on the day of spontaneous term labor. However, both tissue inhibitors of metalloproteinase-1 and -2 levels increased after preterm labor that was induced by group B streptococci. Immunocytochemistry localized matrix metalloproteinase-9 protein to amnion and chorion epithelial and mesenchymal cells and decidual stromal cells. Granular matrix metalloproteinase-9 staining was observed in the connective tissue layer of inflamed fetal membranes. In situ hybridization for messenger RNA confirmed the production of matrix metalloproteinase-9 by amnion and chorion. CONCLUSION: Bacterial- and interleukin-1 beta-induced preterm labor and spontaneous term labor are preceded and accompanied by progressive increases in amniotic fluid matrix metalloproteinase-9 (92 kd) in rhesus monkeys. Amniotic fluid matrix metalloproteinase-9 may serve as a clinical marker for the onset of both preterm and term labor.

Amnion↗
PubMed2002

The role of matrix metalloproteinases in vascular disease.

There is growing interest in the role of matrix metalloproteinases in vascular diseases. These conditions are often characterized by excessive tissue remodelling, and increased matrix metalloproteinase activity has been demonstrated in aneurysms, intimal hyperplasia and atherosclerotic plaque disruption. These enzymes represent a potential target for therapeutic intervention to modify vascular pathology. The core of this review is derived from a MEDLINE database literature search. The review found that there is convincing evidence of increased matrix metalloproteinase activity in a spectrum of vascular disease. Evidence for an imbalance promoting increased matrix degradation is less well documented. However, studies of matrix metalloproteinase inhibition in vascular disease models suggest potential therapeutic benefit. In conclusion, in vivo studies of matrix metalloproteinase inhibition are required to further study the potential for reversal or deceleration of the excessive tissue remodelling that accompanies vascular disorders.

Connective Tissue Diseases↗
PubMed1996

Matrix metalloproteinase expression during mouse peri-implantation development.

PROBLEM: The purpose of this study was to define the temporal expression and to quantitate the mRNA levels of collagenase, 72 kDa, 92 kDa, and membrane-type matrix metalloproteinase during the peri-implantation period of pregnancy in the mouse uterus. Embryonic expression of 72 kDa and 92 kDa matrix metalloproteinases, as well as interleukin 1 alpha, was also investigated. METHODS: Uterine matrix metalloproteinases were detected using gelatin substrate gel electrophoresis (zymography) and reverse-transcription polymerase chain reaction methodology was used to detect and quantitate different mRNA species in the mouse uterus and blastocyst. RESULTS: Collagenase, 72 kDa, and 92 kDa matrix metalloproteinases are developmentally regulated during the peri-implantation period of pregnancy, but membrane-type matrix metalloproteinase appears to be expressed constitutively. Matrix metalloproteinase mRNA levels have been quantitated and confirm the observed developmental expression patterns. Prominent expression of bot 92 kDa matrix metalloproteinase and interleukin 1 alpha was observed in blastocysts during outgrowth while weak expression of the 72 kDa matrix metalloproteinase was detected. CONCLUSIONS: The date provide evidence of matrix metalloproteinase expression in vivo and substantiate their potential role in tissue remodeling prior to and during blastocyst implantation. Expression of interleukin 1 alpha, 92 kDa, and 72 kDa matrix metalloproteinases suggests that these proteins are important for trophoblast invasion associated with implantation of the early embryo.

Animals↗
PubMed2001

Matrix metalloproteinases in skin pathology (Review).

Human tissue is composed in part of cells and in part of amorphous matrix components. Equilibrium exists between the synthesis and degradation of connective tissue under physiological conditions, which serves both the formation and the maintenance of tissue architecture. Synthesis progresses via mesenchymal cells, degradation is controlled by the proteolytic effect of a group of enzymes, which belong to the protein family of matrix metalloproteinases. In biological development, matrix metalloproteinases play an important role in all essential configurative processes in embryo- and histogenesis. As a result of the importance of matrix metalloproteinases in creation of connective tissue, dysregulation with excessive proteolytic activity may result in tissue damage. Histological structural changes are set in relation to the molecular expression pattern of matrix metalloproteinases using matrix relevant diseases of human skin. Discussion includes fibrosing processes, skin inflammations, wound healing, blistering diseases, premature sun-induced skin aging and primary cutaneous malignomas and their metastases.

Animals↗
PubMed2002

Implications for matrix metalloproteinases as modulators of pediatric lung disease.

Matrix metalloproteinases (MMPs) are a large family (>20) of cation-dependent proteinases believed to be important modulators of normal human lung development and potentially harmful mediators of lung damage. Little is known about MMP production and secretion by the lung during childhood or how alterations in MMP levels may be involved in lung damage. We examined endotracheal aspirates from children (<19 years) without lung disease for the presence of MMP activity. Only gelatinase activity was detectable, and inhibitor profiles suggest they represented one or more MMPs. Comparison of gelatinase activity, MMP expression, and MMP activity in children without pulmonary disease with children who required mechanical ventilation for respiratory failure show: 1) gelatinase activity was approximately five- to sixfold higher in respiratory failure; 2) MMP-7, MMP-8, and MMP-9 concentrations and MMP-8 and MMP-9 activities were markedly elevated in respiratory failure; and 3) MMP-7, MMP-8, and MMP-9 levels were significantly correlated in children with lung disease. These studies provide compelling evidence that specific MMPs are present in the diseased lung and may participate in the pathogenesis of pediatric respiratory failure.

Adolescent↗
PubMed1996

Increased matrix metalloproteinase activity and reduced tissue inhibitor of metalloproteinases-1 levels in amniotic fluids from pregnancies complicated by premature rupture of membranes.

OBJECTIVES: It has been suggested that increased matrix metalloproteinases activity promotes the weakening of the amniochorion during normal and premature rupture of membranes. This study was designed to determine whether levels of matrix metalloproteinases and the tissue inhibitor of metalloproteinases-1 in amniotic fluid change in a pattern consistent with this hypothesis. STUDY DESIGN: Gelatinolytic activity, measured by a soluble substrate assay and zymography, and the concentrations of tissue inhibitor of metalloproteinases-1 were estimated in amniotic fluid obtained from (1) normal early gestations, (2) normal term pregnancies with labor, (3) normal term pregnancies without labor, and (4) pregnancies complicated by premature rupture of membranes. The 92 kd type IV collagenase (matrix metalloproteinase-9) was also detected in amniotic fluid by Western blotting. RESULTS: Matrix metalloproteinase activities were higher in amniotic fluid from normal term pregnancies with labor and pregnancies complicated by premature rupture of membranes than from early pregnancies and term gestations without labor. The amniotic fluid from term pregnancies with labor or pregnancies with premature rupture of membranes contained several gelatinases, as revealed by zymography. The major amniotic fluid gelatinolytic activity in premature rupture of membranes and term pregnancies with labor corresponded to matrix metalloproteinase-9. Tissue inhibitor of metalloproteinases-1 concentrations were highest in early-pregnancy amniotic fluid, followed by term gestation with labor, term gestation without labor, and premature rupture of membranes. CONCLUSIONS: Normal labor and premature rupture of membranes are associated with increased levels of matrix metalloproteinases, particularly matrix metalloproteinase-9 in amniotic fluid. Premature rupture of membranes is associated with reduced levels of tissue inhibitor of metalloproteinases-1. The imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 in amniotic fluid may reflect a disorder that promotes premature rupture of membranes.

Amniotic Fluid↗