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PubMed2001

Increased invasion activity of endometrial stromal cells and elevated expression of matrix metalloproteinase messenger RNA in the uterine tissues of mice with experimentally induced adenomyosis.

OBJECTIVE: This study was undertaken to determine whether changes in stromal cell invasiveness and matrix metalloproteinase activity in mouse uterine tissues were involved in the development of adenomyosis that was induced by ectopic pituitary grafting. STUDY DESIGN: The invasion activity of endometrial stromal cells into various kinds of extracellular matrix components was examined in experimentally induced adenomyotic and control uteri in vitro. The effect of an inhibitor of matrix metalloproteinase on the invasion activity was also examined. Differences between the expression of matrix metalloproteinases in adenomyotic and control uteri were examined with the use of degenerate primer-driven reverse transcription-polymerase chain reaction, dot-blot hybridization, and gelatin zymography. RESULTS: Stromal cells that were obtained from adenomyotic uteri markedly invaded the reconstituted basement membrane matrix and gelatin, and the matrix metalloproteinase inhibitor suppressed the invasion. Expression of membrane-type matrix metalloproteinase -14 messenger RNA and gelatinase activity was elevated in accordance with the development of adenomyosis. CONCLUSION: An elevation of the invasion activity of stromal cells into the extracellular matrix is related to the development of adenomyosis; matrix metalloproteinase -14 may play an important role in the invasion of endometrial tissues into the myometrium.

Animals↗
PubMed2003

Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat.

BACKGROUND & AIMS: During hepatic fibrogenesis, the hepatic extracellular matrix changes to fibrillar collagens types I and III, and cirrhosis is believed to produce an irreversible scar. In this study, we investigated whether gene delivery of human matrix metalloproteinase-1, which degrades collagens types I and type III, would attenuate established hepatic fibrosis in the rat, induced by either thioacetamide or bile duct ligation. METHODS: Hepatic fibrosis induced by thioacetamide for 7 weeks was persistent for at least 2 months, even after discontinuation of the treatment. The rats were infected once with a recombinant adenovirus, Ad5MMP-1, into which human pro-human matrix metalloproteinase-1 complementary DNA was packaged, or with a control adenovirus, Ad5LacZ. RESULTS: In Ad5MMP-1-infected, but not in Ad5LacZ-infected, rats, the fibrosis was dramatically attenuated at 2 weeks after the infection. It is interesting to note that the number of activated hepatic stellate cells was also decreased in Ad5MMP-1-infected rats. Moreover, disorganization of the hepatic trabecula, heterogeneity in the size of hepatocytes, and increased dried liver weight were observed only in Ad5MMP-1-treated rats, suggesting that human matrix metalloproteinase-1 stimulated hepatocyte proliferation, which was confirmed by bromodeoxyuridine staining. After 4 weeks, the proliferative effect of human matrix metalloproteinase-1 almost disappeared, but the hepatic fibrosis remained attenuated, whereas the fibrosis in Ad5LacZ-treated rats persisted. Furthermore, the administration of Ad5MMP-1, but not Ad5LacZ, decreased type I collagen and generated a small collagen fragment in hepatic fibrosis induced by bile duct ligation. CONCLUSIONS: Our findings show that transient human matrix metalloproteinase-1 overexpression in the liver effectively attenuates established fibrosis and induces hepatocyte proliferation.

Adenoviridae↗
PubMed1998

Regulated expression of matrix metalloproteinases and TIMP in nephrogenesis.

The roles of the matrix metalloproteinases (MMPs) and their specific inhibitors, the tissue inhibitors of metalloproteinases (TIMP), in embryologic development in general, and in nephrogenesis in particular, have not been fully elucidated. The activities of these enzymes and their inhibitors may be critical in the extensive extracellular matrix remodeling that accompanies the formation of the full complement of mature nephrons in the developing kidney. The temporal and spatial expression of two critical basal lamina modifying enzymes, the 72 kDa gelatinase A (MMP-2) and the 92 kDa gelatinase B (MMP-9), as well as TIMP-1, -2, and -3 molecules were evaluated in the developing rat kidney. Additionally, transcripts for the recently described membrane-associated matrix metalloproteinase, MT1-MMP (MMP-14), which can act as an activating receptor for MMP-2/TIMP-2 complexes (Strongin et al.[1995] J. Biol. Chem. 270:5331-5338) were localized by in situ hybridization. Our immunohistochemical data demonstrate distinct localization of MMP-2 within immature nephron structures undergoing epithelial differentiation, while MMP-9 localizes only to the invading vascular structures within immature glomeruli. In contrast, by in situ hybridization, MMP-2 transcripts localize to the background undifferentiated mesenchyme and not to those structures undergoing epithelial differentiation. In a pattern similar to the MMP-2 protein, MT1-MMP transcripts were found within developing epithelial structures. Neither MMP-2, MMP-9 nor MT1-MMP were detected in mature nephrons. TIMP-2 and -3 follow a pattern of expression similar to the MMP-2 protein. We conclude that MMP-2 and TIMP play important roles in the remodeling of basal laminae associated with the epithelial structures of the developing kidney, that these enzymes are temporally and spatially regulated, and that the co-localization of MT1-MMP to sites of basement membrane remodeling suggests a potential role for this molecule as a receptor for and/or modulator of MMP-2/TIMP complexes.

Animals↗
PubMed2004

[The expression of matrix metalloproteinase-2 and -9 in cervical cancer and a study of their relationship].

OBJECTIVE: To detect the expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in cervical cancer and their correlation with clinicopathologic features. METHODS: With the use of specific monoclonal antibody to human MMP-2 and MMP-9, the formalin-fixed and paraffin-embedded specimens of 62 invasive carcinomas of cervix uteri, 5 carcinomas in situ, 10 normal cervical epithelia and 10 lymph node metastases were detected by immunohistochemical method. RESULTS: MMP-2 and MMP-9 protein expressions in tumor and peritumoral stromal cells were enhanced in invasive carcinoma, compared to those in carcinoma in situ and controls (P < 0.05). There was a low correlation between MMP-2 and MMP-9 (r = 0.34, P < 0.01); the expression level of MMP-9 was higher than MMP-2. The protein expressions of MMP-2 and MMP-9 did not correlate with tumor stage, histological grade or pathological subtype. MMP-9 was correlated with lymph node metastasis and lymphovascular space invasion. CONCLUSION: The over-expression of matrix metalloproteinase-2 and -9 was correlated with invasive behaviour of cervical cancer, MMP-9 was significantly correlated with the lymph node metastasis, it might become a useful prognostic indicator for early cervical cancer.

Adult↗
PubMed2002

Matrix metalloproteinases in cancer.

The extracellular matrix (ECM) holds cells together and maintains the three-dimensional structure of the body. It also plays critical roles in cell growth, differentiation, survival and motility. For a tumour cell to metastasize from the primary tumour to other organs, it must locally degrade ECM components that are the physical barriers for cell migration. The key enzymes responsible for ECM breakdown are matrix metalloproteinases (MMPs). To date, 23 MMP genes have been identified in humans and many are implicated in cancer. ECM degradation by MMPs not only enhances tumour invasion, but also affects tumour cell behaviour and leads to cancer progression. This review highlights recent developments with regard to the cellular and molecular mechanisms of MMPs that influence tumour cell growth, invasion and metastasis.

Animals↗
PubMed2006

Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in macrophages in vivo.

BACKGROUND: Matrix metalloproteinases (MMPs) in inflamed atherosclerotic plaques may contribute to extracellular matrix remodeling and the onset of acute thrombotic complications. METHODS AND RESULTS: To test the hypothesis that optical molecular imaging with the use of an activatable near-infrared fluorescence (NIRF) probe can detect enzymatic action of MMP in atherosclerotic plaques, we used a NIRF substrate for gelatinases (MMP-2/gelatinase-A and MMP-9/gelatinase-B) in apolipoprotein E-deficient (apoE-/-) mice that consumed a high-cholesterol diet for 12 weeks and age-matched apoE+/+ mice as control. The aortas of apoE-/- mice at 24 hours after probe yielded intense NIRF signals, as detected by NIRF reflectance ex vivo, compared with negligible signals in aortas of apoE+/+ mice with/without probe administration or atherosclerotic apoE-/- aortas without probe. Gelatinase inhibitor treatment abolished NIRF signals in apoE-/- mouse aortas ex vivo. Sites of gelatinase activity visualized by NIRF colocalized with macrophage accumulation, immunoreactive MMP-2 and MMP-9, and gelatinolytic activity detected by in situ zymography. Furthermore, fluorescence molecular tomography indicated in vivo that atherosclerotic aortas of apoE-/- mice produced NIRF signals for gelatinase action, whereas aortas of apoE+/+ mice injected with the probe or apoE-/- aortas with no probe exhibited negligible NIRF signals. CONCLUSIONS: These results suggest the feasibility of noninvasively imaging the enzymatic action of MMPs in vivo, an approach that may gauge inflammatory foci in atherosclerosis, assess cardiovascular risk, and evaluate the effects of therapeutic interventions.

Animals↗
PubMed2002

Hepatocarcinoma cell lines down-regulate matrix metalloproteinase-2 expression in human hepatic myofibroblasts.

Matrix metalloproteinases (MMPs) are a family of proteases that degrade extracellular matrix components and are involved in tumor progression and metastasis. We studied the pattern of expression of MMP-2 by human hepatoma cell lines and human hepatic myofibroblasts and its regulation in co-culture between these cell types. MMP-2 expression was studied by zymography and semi-quantitative RT-PCR. The expression of MT1-MMP (involved in MMP-2 activation) was studied by Western blot analysis and RT-PCR and the secretion of TIMP-2 by ELISA and RT-PCR. Myofibroblasts expressed high levels of MMP-2, MT1-MMP and TIMP-2. The hepatoma cell lines HepG2, HuH7 and Hep3B did not express MMP-2 and weakly expressed TIMP-2 and MT1-MMP. In co-culture, no modulation of MT1-MMP or TIMP-2 expression was observed. A strong decrease in myofibroblast MMP-2 expression was seen in the presence of hepatoma cell lines. This was partly reproduced by their conditioned media. We conclude that hepatoma cell lines down-regulate the expression of MMP-2 by myofibroblasts.

Carcinoma, Hepatocellular↗
PubMed2003

A study on angiogenesis-related matrix metalloproteinase networks in primary hepatocellular carcinoma.

Matrix metalloproteinases (MMPs) specially degrade extracellular matrix (ECM) proteins and are involved in tissue remodeling and angiogenesis. Therefore, studies on the role of MMPs in the carcinogenesis, proliferation and infiltration of hepatocellular carcinoma (HCC) may greatly contribute to the development of a new clinically applicable therapeutic approach. In the present study, we immunologically examined the expression rates of various MMPs including MMP-2, 3, 7, 9, membrane type 1-MMP (MT1-MMP), and MT2-MMP in the cancerous and noncancerous areas of resected tumor specimens from 30 patients with primary HCC. The rate of MMP-2 expression was high for both cancerous and noncancerous areas. However, the expression rates of MMP-3, MT1-MMP, and MT2-MMP were significantly higher in cancerous areas than in noncancerous areas. Next, we examined the clinicopathologic features such as the number of tumor nodules, maximal tumor size, presence or absence of capsular infiltration and portal vein invasion, histological grades of HCCs, state of noncancerous areas (chronic hepatitis: CH or liver cirrhosis: LC), and short-term recurrence after resection (within six months). In conclusion, it was found that three main networks of MMPs are predominantly involved in the case of HCC, that is, MMP-2 and MT1-MMP in the carcinogenesis and progression, MMP-7 and MMP-9 in the capsular infiltration and portal vein invasion, as well as MMP-3 and MMP-7 in the progression of HCC. Furthermore, MT1-MMP appeared to be the most important factor in HCC because of its widespread pattern of expression.

Carcinoma, Hepatocellular↗
PubMed2005

Distinct modes of collagen type I proteolysis by matrix metalloproteinase (MMP) 2 and membrane type I MMP during the migration of a tip endothelial cell: insights from a computational model.

Matrix metalloproteinases (MMPs) are a family of enzymes responsible for the proteolytic processing of extracellular matrix (ECM) structural proteins under physiological and pathological conditions. During sprouting angiogenesis, the MMPs expressed by a single "tip" endothelial cell exhibit proteolytic activity that allows the cells of the sprouting vessel bud to migrate into the ECM. Membrane type I matrix metalloproteinase (MT1-MMP) and the diffusible matrix metalloproteinase MMP2, in the presence of the tissue inhibitor of metalloproteinases TIMP2, constitute a system of proteins that play an important role during the proteolysis of collagen type I matrices. Here, we have formulated a computational model to investigate the proteolytic potential of such a tip endothelial cell. The cell expresses MMP2 in its proenzyme form, pro-MMP2, as well as MT1-MMP and TIMP2. The interactions of the proteins are described by a biochemically detailed reaction network. Assuming that the rate-limiting step of the migration is the ability of the tip cell to carry out proteolysis, we have estimated cell velocities for matrices of different collagen content. The estimated velocities of a few microns per hour are in agreement with experimental data. At high collagen content, proteolysis was carried out primarily by MT1-MMP and localized to the cell leading edge, whereas at lower concentrations, MT1-MMP and MMP2 were found to act in parallel, causing proteolysis in the vicinity of the leading edge. TIMP2 is a regulator of the proteolysis localization because it can shift the activity of MT1-MMP from its enzymatic toward its activatory mode, suggesting a tight mechanosensitive regulation of the enzymes and inhibitor expression. The model described here provides a foundation for quantitative studies of angiogenesis in extracellular matrices of different compositions, both in vitro and in vivo. It also identifies critical parameters whose values are not presently available and which should be determined in future experiments.

Cell Movement↗
PubMed2005

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes.

OBJECTIVE: We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes. STUDY DESIGN: We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks' gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed. RESULTS: The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P = .94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P = .03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P = .03). CONCLUSIONS: The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.

Adult↗
PubMed1997

[Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase by myofibroblasts--morphological study on corneal wound healing].

The matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) regulate the extracellular matrix and are important in the process of connective tissue remodeling. In this study, we investigated the expression of MMPs and TIMP-2 by myofibroblasts (MF) originating from keratocytes during the healing of alkali-burned and lacerated rabbit corneas. In light and/or electron microscopic immunohistochemistry, the MMP-1, 2, 9 and TIMP-2 antibodies reacted with MF in both types of corneal wounds. The clear expression of MMP-1 and the relatively faint immunoreaction of MMP-2 were observed in both types of healing from one week after wounding, while MMP-9 appeared from 3 weeks after injury. In addition, the levels of MMP-2 and 9 were increased from 4 weeks after alkali-burned injury. The clear expression of TIMP-2 was observed from 1 week after both types of wounds. These findings indicate that MF is deeply involved in degrading some of the key matrix proteins (such as type I collagen), and may play an important role in tissue remodeling in corneal wounds through production of MMPs and TIMP.

Animals↗
PubMed2000

Structural analysis and promoter characterization of the human membrane-type matrix metalloproteinase-1 (MT1-MMP) gene.

Membrane type-1 matrix metalloproteinase (MT1-MMP) degrades extracellular matrix components directly and indirectly by activation of other matrix metalloproteinases (MMPs). In the present study, we have isolated and characterized the human MT1-MMP gene and its promoter. The gene consists of 10 exons and nine introns spanning more than 10 kilobases (kb). The locations of two exon-intron splicing sites are distinct from the preserved positions among other known MMP genes. Primer extension and RNAse and S1 nuclease protection analyses indicated that there are four major and several minor transcription start sites. The 5'-flanking sequence of the gene contains putative regulatory elements, including one Sp-1 site and four CCAAT-boxes, whereas there is no TATA-box. The Sp-1 binding site was functional, as shown by gel shift and supershift analyses. Transfection studies with promoter constructs containing 0.1 to 7.2 kb of 5'-flanking sequence coupled to a luciferase reporter gene indicated that the promoter contains additional positive and negative regulatory sequences. Deletion of the Sp-1 binding site by site-directed mutagenesis reduced luciferase activity by about 90%, demonstrating the crucial role of this element in maintaining MT1-MMP transcription. Our findings indicate that the human MT1-MMP promoter has distinctive structural and functional features compared with other MMP genes, which may lead to a unique expression pattern and regulation during physiological and pathological processes.

Base Sequence↗
PubMed2003

Identification, purification and partial characterization of tissue inhibitor of matrix metalloproteinase-2 in bovine pulmonary artery smooth muscle.

Bovine pulmonary artery smooth muscle possesses the tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) as revealed by Western immunoblot study of its cytosol fraction with bovine polyclonal TIMP-2 antibody. This potent polypeptide inhibitor of matrix metalloproteinases (MMPs) was purified to homogeneity from cytosol fraction of bovine pulmonary artery smooth muscle. This inhibitor was purified by ammonium sulfate precipitation followed by gelatin sepharose and lentil lectin sepharose affinity chromatography and continuous elution electrophoresis by Prep Cell Model 491 (Bio-Rad, USA). SDS-PAGE revealed that the inhibitor has an apparent molecular mass of 21 kDa and was confirmed as TIMP-2 by (i) Western immunoblot assay using bovine polyclonal TIMP-2 antibody; and also by (ii) amino terminal amino acid sequence analysis of the purified inhibitor is found to be identical with TIMP-2 obtained from other sources. The purified 21 kDa inhibitor was found to be active against matrix metalloproteinase-2 (MMP-2, 72 kDa gelatinase) and matrix metalloproteinase-9 (MMP-9, 92 kDa gelatinase), the ambient MMPs in the pulmonary artery smooth muscle. The inhibitor was also found to be sensitive to the activated 72 kDa gelatinase-TIMP-2 complex and also active human interstitial collagenase. By contrast, it was found to be insensitive to the serine proteases: trypsin and plasmin. The inhibitor was heat and acid resistant and it had the sensitivity to trypsin degradation and reduction-alkylation. Treatment of the inhibitor with hydrogen peroxide, superoxide generating system (hypoxanthine plus xanthine oxidase) and peroxynitrite inactivated the inhibitor.

Ammonium Sulfate↗
PubMed2003

Expression of matrix metalloproteinases in vasculitic neuropathy.

The aim of this study was to investigate the expression pattern and cellular source of matrix metalloproteinases (MMP) in vasculitic neuropathy. Matrix metalloproteinases are endopeptidases degrading components of extracellular matrix proteins, and they have been implicated in the pathogenesis of inflammatory demyelination. They are induced by cytokines, secreted by inflammatory cells, and enhance T cell migration. Vasculitic neuropathy occurs as a component of systemic vasculitis or as an isolated angiitis of the peripheral nervous system, and T cell-mediated inflammation is detected in its pathogenesis. Nerve biopsy sections of eight patients with nonsystemic vasculitic neuropathy (NSVN) and four with systemic vasculitic neuropathy were examined for the presence of CD4+, CD8+, and CD68+ cells and immunohistochemically for MMP-2 and MMP-9 expression. Nerve biopsies of eight patients with noninflammatory neuropathy were used as a control group. Semiquantitative polymerase chain reaction analysis was performed to detect MMP-2 and MMP-9 mRNA. The predominant cells were CD8+ and CD68+ T cells. Expression of MMP-9, but not MMP-2, was increased in perivascular inflammatory infiltrate in nerve tissues of vasculitic neuropathy patients. This MMP-9 expression correlated positively with immunostaining of CD8+ T cells. No difference was detected between immunostaining patterns of nonsystemic and systemic vasculitic neuropathies with the antibodies used, except in MMP-9 immunostaining, which was found to be enhanced in NSVN group. Polymerase chain reaction analysis revealed elevated mRNA levels of MMP-9 and MMP-2 compared with controls, but this did not reach statistical significance. Our results imply a pathogenic role for MMP-9 secreted from CD8+ cells in vasculitic neuropathy.

Adolescent↗
PubMed2002

Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9).

The matrix metalloproteinases (MMPs) form an enzyme family of which gelatinase B (MMP-9) represents the largest and most complex member. We focus here on the biochemical properties, regulation, and functions of gelatinase B. The tight regulation of gelatinase B activity is highly complex and is established at five different levels. The transcription of the gelatinase B-gene depends on various cis-elements in its gene promotor and is induced or repressed by a large variety of soluble factors, including cytokines, growth factors, and hormones and by cellular contacts acting through specific signaling pathways. The specific regulation of its secretion occurs in cells storing gelatinase B in granules. After secretion, progelatinase B must be activated through an activation network. The enzyme activity is further regulated by inhibition and by other mechanisms, such as fine-tuning and stabilization by glycosylation. The ability of gelatinase B to degrade components of the extracellular matrix and to regulate the activity of a number of soluble proteins confers an important role in various physiological and pathological processes. These include reproduction, growth, development, inflammation, and vascular and proliferative diseases.

Animals↗
PubMed2000

Immunohistochemical detection of membrane-type-1-matrix metalloproteinase in colorectal carcinoma.

We investigated whether the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was consistent with the proposed roles of these proteins in promoting metastasis in colorectal cancer. The expression of MT1-MMP was significantly more frequent in deeply invasive carcinomas (P = 0.007) and in cases of vascular invasion (P = 0.02). The frequency of detection of MMP-2 in the stroma was much greater in vascular invasion-positive cases (42%) than in negative cases (20%; P = 0.02). The rate of detection of TIMP-2 in tumour cell cytoplasm increased with the depth of invasion (P = 0.03). TIMP-2 in the stroma was found more frequently in tumours with lymphatic invasion and lymph node metastasis (P < 0.05). Significant correlations were found between detection of MT1-MMP and MMP-2 in tumour cell cytoplasm (P < 0.05), of MT1-MMP and TIMP-2 in tumour cell cytoplasm (P < 0.01), and of MMP-2 and TIMP-2 in tumour cell cytoplasm (P < 0.01). Immunohistochemical detection of MT1-MMP and TIMP-2 might be useful for monitoring infiltration in colorectal carcinoma but is not correlated with distant metastases.

Adenocarcinoma↗
PubMed2000

Calculation and prediction of binding free energies for the matrix metalloproteinases.

The zinc-dependent matrix metalloproteinases are drug targets of interest for diseases ranging from arthritis to cancer. Unfortunately, the use of computational rational drug design has been limited by the challenges introduced by the zinc center. We present an extension of the MM/PB/SA methodology which allows us to calculate the relative binding energies of six known nanomolar carboxylate ligands of MMP-1. We are able to rank the neutral and charged ligands correctly. We further illustrate the utility of our approach by modifying the best-binding ligand of our set and predicting a better binding ligand.

Benzyl Compounds↗
PubMed2005

Role of matrix metalloproteinases in preterm labour.

Extracellular matrix homeostasis is a key process in the maintenance of the tensile strength of the amniochorion. This tensile strength guarantees the role of the membranes as a physical and functional boundary for the fetus during human pregnancy. Pathological rupture of these structures before 37 completed weeks of gestation is known as preterm prelabour rupture of the membranes (PPROM) and it is a major cause of spontaneous preterm labour and preterm birth. A mechanism involving the activation of matrix metalloproteinases (MMP)-9, a 92-kDa type IV collagenase, as an essential mediator of tissue damage is under investigation. The proposed mechanism involves the abnormal expression and activity of MMP-9 with subsequent connective tissue degradation taking place at a time that does not synchronise with other events of labour. The local physiological signal by amniochorion cells to induce MMP-9 expression is not known, but bacterial products and/or the proinflammatory cytokines, IL-1beta and TNF-alpha, as paracrine or autocrine signals may trigger these processes in pregnancies complicated with intra-amniotic infection. These signalling pathways indicate complex cooperative and bidirectional communications between amnion and choriodecidua in response to bacterial products, which include intermembranous cytokine traffic and signalling between tissues. Products secreted in culture by amniochorion and choriodecidual leucocytes, obtained from women who delivered following normal labour in the absence of infection, condition a specific microenvironment that induces collagen degradation in fetal membranes. Further characterisation of the role of choriodecidual leucocytes in the control of extracellular matrix degradation in amniochorion is currently under way.

Extraembryonic Membranes↗