Specific expression of PP5/TFPI-2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization

Udagawa, Koichi; Miyagi, Yohei; Hirahara, Fumiki; Miyagi, Etsuko; Nagashima, Yoji; Minaguchi, Hiroshi; Misugi, Kazuaki; Yasumitsu, Hidetaro; Miyazaki, Kaoru

doi:10.1016/s0143-4004(98)90011-x

Cited by 59 publications

(61 citation statements)

References 29 publications

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“…Cytotrophoblast differentiation and the maintenance of intervillous flow has been shown to depend on PP5/TFP12, a Kunitz-type proteinase inhibitor, identical to TF inhibitor-2. 30 Thus, an influence of TF expression in placental tissue could conceivably influence cytotrophoblast differentiation.…”

Section: Discussionmentioning

confidence: 99%

AT ₁ Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor

et al. 2000

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Background-We recently described autoantibodies (angiotensin-1 receptor autoantibodies, AT 1 -AA) directed at the AT 1 receptor in the serum of preeclamptic patients, whose placentas are commonly infarcted and express tissue factor (TF). Mechanisms of how AT 1 -AA might contribute to preeclampsia are unknown. We tested the hypothesis that AT 1 -AA cause vascular smooth muscle cells (VSMC) to express TF. Methods and Results-IgG from preeclamptic patients containing AT 1 -AA was purified with anti-human IgG columns.AT 1 -AA were separated from the IgG by ammonium sulfate precipitation. We transfected Chinese hamster ovary cells overexpressing the AT 1 receptor with TF promoter constructs coupled to a luciferase reporter gene. VSMC were obtained from human coronary arteries. Extracellular signal-related kinase activation was detected by an in-gel kinase assay. AP-1 activation was determined by electromobility shift assay. TF was measured by ELISA and detected by immunohistochemistry. Placentas from preeclamptic women stained strongly for TF, whereas control placentas showed far less staining. We proved AT 1 -AA specificity by coimmunoprecipitating the AT 1 receptor with AT 1 -AA but not with nonspecific IgG. Angiotensin (Ang) II and AT 1 -AA both activated extracellular signal-related kinase, AP-1, and the TF promoter transfected VSMC and Chinese hamster ovary cells, but only when the AP-1 binding site was present. We then demonstrated TF expression in VSMC exposed to either Ang II or AT 1 -AA. All these effects were blocked by losartan. Nonspecific IgG or IgG from nonpreeclamptic pregnant women had a negligible effect. Conclusions-We conclude that AT 1 -AA and Ang II both stimulate the AT 1 receptor and initiate a signaling cascade resulting in TF expression. These results show an action of AT 1 -AA on human cells that could contribute to the pathogenesis of preeclampsia.

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Section: Discussionmentioning

confidence: 99%

AT ₁ Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor

et al. 2000

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“…1 Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor 2 synthesized by endothelial cells (ECs), smooth muscle cells (SMCs), and syncytiotrophoblasts, 3,4 which associates through ionic interactions 5 with the extracellular matrix (ECM), 6 and inhibits trypsin, plasmin, and plasma kallikrein among others. 7 The ECM is essential for the integrity of the cardiovascular system.…”

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Adenovirus-Mediated Expression of Tissue Factor Pathway Inhibitor-2 Inhibits Endothelial Cell Migration and Angiogenesis

Ivanciu

Gerard

Tang

et al. 2007

ATVB

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Objective-Extracellular matrix (ECM) remodeling during angiogenesis is accomplished through plasmin-dependent pericellular proteolysis and through the action of matrix metalloproteinases (MMPs). Because tissue factor pathway inhibitor-2 (TFPI-2), a Kunitz-type protease inhibitor with prominent ECM localization, inhibits plasmin and MMPs activity, we investigated the role of TFPI-2 in endothelial cell (EC) migration and angiogenesis. Methods and Results-Real-time polymerase chain reaction and immunostaining showed that the expression of TFPI-2 mRNA and protein was upregulated in migrating ECs. The effect of TFPI-2 on angiogenesis was studied in mouse models of Matrigel and polyvinylalcohol sponge implants by overexpressing TFPI-2 through infection with a replication-deficient adenovirus (AdTFPI-2). Using (immuno)fluorescence and confocal microscopy we observed that TFPI-2 reduced neovascularization and promoted ECM deposition. Lateral cell migration and capillary tube formation in vitro also were impaired by TFPI-2, a process reversed by anti-TFPI-2 antibodies. Increased apoptosis occurred both in AdTFPI-2-treated ECs and in the mouse implants. Zymography and assays in the absence of plasminogen confirmed plasmin inhibition as a main mechanism through which TFPI-2 inhibits EC migration. Conclusions-Our data suggest that TFPI-2 may be an important regulator of aberrant angiogenesis associated with tumor growth/metastasis, cardiovascular diseases, chronic inflammation, or diabetes. Key Words: TFPI-2 Ⅲ angiogenesis Ⅲ endothelial cell Ⅲ adenovirus gene delivery Ⅲ mouse model P roteinase inhibitors are involved in blood coagulation, fibrinolysis, angiogenesis, wound healing, and tumor invasion. 1 Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor 2 synthesized by endothelial cells (ECs), smooth muscle cells (SMCs), and syncytiotrophoblasts, 3,4 which associates through ionic interactions 5 with the extracellular matrix (ECM), 6 and inhibits trypsin, plasmin, and plasma kallikrein among others. 7 The ECM is essential for the integrity of the cardiovascular system. ECs use the matrix as scaffolding during invasion, but they also degrade it to provide space for new capillaries. Serine proteases belonging to the plasminogen activator (PA)/plasmin system and (membrane-type)-matrix metalloproteinases [(MT)-MMPs] play major roles in all the steps of angiogenesis 8 : vessel sprouting, cell migration, tube formation, survival, generation of matrikines as angiogenesis inhibitors, and vessel stabilization/maturation and remodeling. 9,10 Matrix metalloproteinase (MMP)-2, MMP-9, and MT1-MMP switch on neovascularization through degradation of the endothelial and interstitial matrix, and activation of growth factors (reviewed in 10 ). Protease activities are controlled by specific activation mechanisms and inhibitors, of which tissue inhibitors of MMPs and serpins, like PA inhibitors (PAIs), represent major classes. MMPs are secreted as inactive zymogens that are activated by other proteinases, s...

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“…In addition, direct inhibition of MMP1, -2, -9, and -13 activities have been reported (14). TFPI-2 is secreted by several cell types, including endothelial cells (15), smooth muscle cells, fibroblasts (16), keratinocytes (17), and syncytiotrophoblasts (18). Its preferential association to the extracellular matrix (ECM) has been documented (19), and several reports suggest a pivotal role of TFPI-2 in the maintenance and regulation of ECM remodeling.…”

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ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2

Torres-Collado

Kisiel

Iruela‐Arispe

et al. 2006

Journal of Biological Chemistry

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ADAMTS1 is an extracellular metalloproteinase known to participate in a variety of biological processes that includes inflammation, angiogenesis, and development of the urogenital system. Many of its functions rely on its catalytic activity, which thus far has been limited to the cleavage of the matrix proteoglycans aggrecan and versican. However, it is likely that other substrates exist. Using a yeast two-hybrid screen, we identified the Kunitz-type inhibitor, tissue factor pathway inhibitor-2 (TFPI-2), as a binding partner of ADAMTS1. The interaction was confirmed by several biochemical and cell-based assays. In addition, our studies revealed alterations in the pattern of TFPI-2-secreted isoforms and in its extracellular location caused by the specific action of ADAMTS1. Interestingly, we found that TFPI-2 is a novel substrate of ADAMTS1. The cleavage removes a protease-sensitive C-terminal region in TFPI-2, altering its binding properties. The proposed role of TFPI-2 as a maintenance factor of extracellular remodeling suggests the indirect function of ADAMTS1 as an additional homeostatic player by its ability to alter the extracellular location of TFPI-2 and, therefore, to disrupt the remodeling machinery, a phenomenon directly associated to pathologies such as atherosclerosis and tumor progression.The extracellular milieu has been recognized as a dynamic scenario that directly influences proliferation, survival, migration, and biosynthetic activities of cells. The constituents of this extracellular environment include growth factors, chemokines, cell surface proteins, and an extensive list of matrix components with structural and signaling properties. Matrix proteases and their respective inhibitors are also important components of the extracellular milieu with the added value that these molecules modify, degrade, or inflict functional alterations to most of the components previously listed (1). In fact, modification of extracellular components by processing and/or proteolysis is a frequent event during morphogenesis and tissue repair and, in an altered manner, during the progression of various pathological conditions (2).The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases includes a group of 19 secreted enzymes with a more restricted spectrum of catalytic activities than the well known matrix metalloproteinases (MMP) 2 (3). ADAMTS1, the first member described (4), has been shown to display anti-angiogenic properties (5). Systemic deletion of adamts1 in mice resulted in multiple defects in the urogenital system (6, 7). The enzyme is known to have catalytic activity toward matrix proteoglycans, particularly versican and aggrecan (8,9).Mechanistically, it is not evident that the outcomes of the gene-deletion studies can be linked with the catalytic profile known for this enzyme. Thus, it is possible that either other domains contribute to the spectrum of biological functions and/or that additional biologically relevant substrates are yet to be identified. The modular...

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Specific expression of PP5/TFPI-2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization

Cited by 59 publications

References 29 publications

AT ₁ Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor

AT ₁ Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor

Adenovirus-Mediated Expression of Tissue Factor Pathway Inhibitor-2 Inhibits Endothelial Cell Migration and Angiogenesis

ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2

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Specific expression of PP5/TFPI-2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization

Cited by 59 publications

References 29 publications

AT 1 Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor

AT 1 Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor

Adenovirus-Mediated Expression of Tissue Factor Pathway Inhibitor-2 Inhibits Endothelial Cell Migration and Angiogenesis

ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2

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AT ₁ Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor

AT ₁ Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor