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

The placenta is formed by developing trophoblast cells to facilitate fluid, gas and nutrient exchange with the mother. Inappropriate trophoblast responsiveness can lead to life threatening complications during pregnancy including intrauterine growth retardation, pre-eclampsia, spontaneous abortion and malignancy that could lead to fetal loss. Transforming growth factor beta (TGFbeta) is a multifunctional cytokine required for embryonic development and is an important regulator of human trophoblast function. Although TGFbeta is critical for placental and embryonic development, there are currently no established TGFbeta-responsive human trophoblast-derived cell lines available to study the mechanisms by which TGFbeta regulates trophoblast function. Our studies have examined the transformed human trophoblast-derived cell line, ED27, to determine if it is responsive to TGFbeta. Our data indicate that TGFbeta dose responsively and reversibly inhibits cell growth in ED27 cells and induces classic TGFbeta response genes, fibronectin and plasminogen activator inhibitor 1 (PAI-1). TGFbeta also induces an inhibitor of trophoblast invasion, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in ED27 cells. Our studies have identified a human trophoblast-derived cell line that parallels isolated primary human trophoblasts in their responses to TGFbeta. This cell line may provide us with the opportunity to determine TGFbeta-mediated responses on human trophoblast functions not previously possible.
Placenta 2001 May
PMID:Characterization of a TGFbeta-responsive human trophoblast-derived cell line. 1171 79

Deficient trophoblast invasion is a major feature of pre-eclampsia. In vitro studies suggest that in normal pregnancy, maternal cells may play a role in controlling trophoblast invasion, although the exact nature of the regulatory interactions between these cells is not fully understood. To examine the effect of maternal-placental cell interactions on matrix metalloproteinase (MMP) secretion and endovascular cytotrophoblast migration in normal pregnancy and in pre-eclampsia, we performed co-culture experiments using cytotrophoblasts from normal pregnancies, together with decidual endothelial cells from both normal and preeclamptic pregnancies. Cells were incubated on semi-permeable membranes with or without phorbol 12-myristate 13-acetate (PMA). Results showed that third trimester cytotrophoblasts are migratory under basal conditions and display a different MMP profile from decidual endothelial cells. Co-culture did not damage either cell type and resulted in reduced latent MMP-9 secretion and reduced cytotrophoblast migration. Although PMA upregulated MMPs in decidual endothelial cells, it had no effect on cytotrophoblast MMP secretion. PMA, however, reduced cytotrophoblast migration. Pre-eclamptic decidual endothelial cells showed reduced MMP-1 secretion, but overall were not different in co-culture from normal endothelial cells. This study demonstrates the effectiveness of a bilayer co-culture model to study maternal-foetal cell interactions and provides evidence that maternal cells may contribute to the control of endovascular cytotrophoblast invasion.
Placenta 2003 Apr
PMID:In vitro migration of cytotrophoblasts through a decidual endothelial cell monolayer: the role of matrix metalloproteinases. 1265 3

In the endotheliochorial placenta of the cat, the maternal surface epithelium and parts of the connective tissue have to be removed to bring the fetal blood vessels in close contact to the maternal capillaries. The composition of the extracellular matrix (ECM) in the feline uterus is not known and it is still not clear if and which parts of the maternal ECM persist during gestation in the placental labyrinth. We demonstrated various extracellular matrix components (collagen types I, III, IV, and laminin) and matrix metalloproteinases (MMP-1, -2, -13) using immunohistochemistry and studied the distribution of intermediate filaments (vimentin, cytokeratin) and alpha-smooth muscle actin (SMA) in the placental girdle on specimens of different stages of gestation. Collagen types I and III were mainly present in the fetal chorionic lamellae whereas diminished in the maternal placental labyrinth part. Collagen IV and laminin were expressed in fetal basement membranes and mesenchyme. Maternal endothelial cells and stromal cells showed a positive immunoreaction for anti-collagen type IV and laminin. MMP-2 was identified in the maternal stroma, including decidual cells. Endothelia of maternal blood vessels within the labyrinth contained MMP-1, -2 and -13, probably associated with angiogenesis. In the trophoblast MMP-1 and -13 were demonstrated. Maternal stem vessels were accompanied by a thick layer of syncytiotrophoblast. Around these vessels, collagen type I and SMA were present in a periendothelial region between the endothelium and the trophoblast. These findings indicate that a strictly regulated balance between ECM deposition and ECM degradation in the feline placental labyrinth is necessary for proper placental development and function.
Placenta
PMID:Extracellular matrix components and matrix degrading enzymes in the feline placenta during gestation. 1633 74

Shortened gestation is a major cause of infant mortality and morbidity. Evidence from both human and animal studies suggests that essential fatty acids of the n-6 and n-3 series play important and modifiable roles in gestational duration. We examined the influence of linolenic acid (LnA) vs. docosahexaenoic acid (DHA) on rat reproductive tissue prostaglandin (PG) and matrix metalloproteinase (MMP) indices of gestational duration. By varying the oil source of the diet, AIN-93G diets were constructed to provide either 0.7 energy % (en%) LnA, the current US intake of n-3 fatty acids, or 0.7 en% DHA. In addition, enhanced levels of 2.0 en% LnA or 2.0 e% DHA diets were also constructed. All diets contained approximately 6.0 en% linoleic acid (LA), the current US intake of LA. Four groups of 10 female rats were time-mated and fed the respective diets from conception through Day 20 of gestation. Day 20 uterus and placenta DHA were significantly increased by 160-180% by the 0.7 en% DHA diet, and by 250-350% by the 2.0 en% DHA diets in comparison to 0.7 en% LnA diet. DHA diets also significantly reduced uterus and placenta arachidonic acid content. Day 20 placenta and uterus PGE(2) and placenta PGF(2alpha) production rates were significantly reduced by 27-47% in the 0.7 en% DHA group in comparison to 0.7 en% LnA. Increasing LnA to 2.0 en% was without effect. Providing DHA at the enhanced 2.0 en% did not significantly enhance the suppression of PG production. Placenta active MMP-2 and active MMP-9 (gelatinase) production was suppressed significantly by 30-43% in the 0.7 en% DHA group in comparison to the 0.7 en% LnA group, and 2.0 en% DHA did not enhance this suppression. Placenta collagenase activity comprising the sum of MMP-1, MMP-8 and MMP-13 was also suppressed by 60% in the 0.7 en% DHA diet group with no additional effect with 2.0 en% DHA provision. These results suggest that substituting DHA for LnA even at the current US n-3 fatty acid intake of 0.7 en% is effective in suppressing indices of premature delivery and shortened gestation. Increasing LnA intake by 3-fold to 2.0 en% is not effective. The form of dietary n-3 fatty acid, DHA vs. LnA, appears to be more important than the amount.
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PMID:Dietary docosahexaenoic acid alters pregnant rat reproductive tissue prostaglandin and matrix metalloproteinase production. 1645 97

Placental trophoblasts are an important source of endocrine, paracrine and autocrine acting hormones. The aim of the present study was to establish and evaluate a tissue culture model for bovine trophoblasts to study regulation of key genes of steroid hormone synthesis. Trophoblast cells were isolated from cotyledons by collagenase disaggregation and subsequent percoll density gradient centrifugation. The cells were seeded on collagen coated dishes and incubated for up to seven days. The cells were characterized for the presence of mesenchymal vimentin and epithelial cytokeratin filaments and for Dolichos biflorus agglutinin (DBA) binding, a marker for differentiated trophoblast giant cells. Transcripts of Hsd3b, Cyp17 and Cyp19 encoding 3beta-HSD, P450c17 and P450arom, the key enzymes of progesterone, androgen, and oestrogen biosynthesis, respectively, and of Csh1 encoding the trophoblast-specific hormone placental lactogen (PL) were measured by qPCR. Uninucleate cotyledonary epithelial cells and bi- and trinucleate trophoblast giant cells efficiently formed a dense cell layer on the collagen coated dishes within 24 h. Bi- and trinucleate cells showed DBA binding and weak or undetectable cytokeratin immunoreactivity. Vimentin-positive, fibroblast-like cells were found on top of this cell layer. Cyp19 transcripts were found in freshly dissociated but not in cultured cells. Cyp17 expression continuously increased, Hsd3b transcripts largely and rapidly increased during the first days in culture, followed by a decline after three days, whereas Csh1 decreased towards day seven. Serum free culture conditions significantly enhanced Cyp17 and Csh1 but not Hsd3b expression. The data indicate that collagen is a favourable substrate for cultured binucleate trophoblast giant cells. The cells represent an in vitro model to study the regulation of key genes of placental progesterone and androgen but not of oestrogen biosynthesis.
Placenta 2008 Jun
PMID:Cultured bovine trophoblast cells differentially express genes encoding key steroid synthesis enzymes. 1845 33

The urokinase plasminogen activator (uPA) system plays pivotal roles in cell invasion, adhesion and migration. Roles for uterine natural killer (uNK) cells in regulating extravillous trophoblast (EVT) invasion and spiral artery remodeling have been proposed. Placental bed biopsies from early pregnancy were obtained from three gestational age groups (8-10, 12-14 and 15-20 weeks). Total caseinase activity in the placental bed was studied using casein in situ zymography. Localisation of uPA, uPA receptor (uPAR), plasminogen activator inhibitor (PAI)-1 and -2 in the placental bed was investigated by immunohistochemistry. CD56(+) uNK cells were separated from collagenase-digested decidual cells using an immunomagnetic technique, and uPA activity was measured in isolated cell culture supernatants by casein/plasminogen gel zymography (8-10 and 12-14 weeks' gestation, n=10 each group). uPAR in cell lysates and PAI-1 and -2 secretion in supernatants were measured by Western blotting. Caseinase activity was stronger in decidua than myometrium as shown by in situ zymography. uPA localised strongly to uNK cells, especially at 8-10 weeks. Moderate uPAR localisation on uNK cells also observed. There was very weak immunostaining of uNK cells for PAI-1 and PAI-2. In casein gel zymography, uPA activity was similar in uNK cell culture supernatant compared with total unseparated decidual cells. uPAR in uNK cell lysates was significantly stronger than in total decidual cell lysates. PAI-1 and PAI-2 were not detected in uNK cell culture supernatants by Western blot analysis. These results suggest that uNK cells may regulate EVT invasion and spiral artery remodeling via the uPA system.
Placenta 2009 May
PMID:The urokinase plasminogen activator (uPA) system in uterine natural killer cells in the placental bed during early pregnancy. 1927 41


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