Intentional endometrial injury enhances angiogenesis through increased production and activation of MMP-9 by TNF-α and MMP-3 in a mouse model

2021 ◽  
Vol 27 (10) ◽  
Author(s):  
Yi-An Tu ◽  
Chia-Hung Chou ◽  
Po-Kai Yang ◽  
Chia-Tung Shun ◽  
Wen-Fen Wen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mouse Model ◽  
Matrix Metalloproteinase ◽  
Active Form ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Endometrial Injury ◽  
Tnf Α ◽  
Endometrial Scratching ◽  
Endometrial Epithelial Cells

Abstract There have been reports of improved pregnancy rates after performing intentional endometrial injuries, also known as endometrial scratching, in patients with recurrent implantation failure. In our previous study on intentional endometrial injury, we found an increased expression of matrix metalloproteinase (MMP)-3 following induced injuries to the mice endometrium. In the current study, we further examine whether the rise in MMP-3 could contribute to increased angiogenesis. Female C57B1/6 mice were obtained at 12 weeks of age, and intentional endometrial injuries were induced mechanically in the left uterine horns. Using the appropriate media, uterine-washes were performed on the injured and uninjured (control) horns of the harvested uteri. The uterine tissues were further processed for tissue lysates, histopathology and immunohistochemistry. The results show that intentional endometrial injuries caused an increase in secreted LPA in the injured horns, which were detected in the uterine-washes. In addition, LPA induced increased production of TNF-α in human endometrial epithelial cells (hEEpCs). Furthermore, TNF-α appeared to induce differential and cell-specific upregulation of the MMPs: MMP-3 was upregulated in the epithelial (hEEpCs), while MMP-9 was upregulated in the endothelial cells (human endometrial endothelial cells; hEEnCs). The upregulation of MMP-3 appeared to be necessary for the activation of MMP-9, whose active form stimulated the formation of vessel-like structure by the hEEnCs. The results of this study suggest that there may be enhanced angiogenesis following intentional endometrial injuries, which is mediated in part by TNF-α-induced and MMP-3-activated MMP-9 production.

scholarly journals Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes

2021 ◽  
Vol 23 (1) ◽  
pp. 221
Author(s):  
Vanesa Palau ◽  
Josué Jarrín ◽  
Sofia Villanueva ◽  
David Benito ◽  
Eva Márquez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mouse Model ◽  
High Fat Diet ◽  
Macrophage Infiltration ◽  
Creatinine Ratio ◽  
Wild Type ◽  
High Fat ◽  
Tnf Α ◽  
Galectin 3 ◽  
Factor Α

Disintegrin and metalloproteinase domain 17 (ADAM17) activates inflammatory and fibrotic processes through the shedding of various molecules such as Tumor Necrosis Factor-α (TNF-α) or Transforming Growht Factor-α (TGF-α). There is a well-recognised link between TNF-α, obesity, inflammation, and diabetes. In physiological situations, ADAM17 is expressed mainly in the distal tubular cell while, in renal damage, its expression increases throughout the kidney including the endothelium. The aim of this study was to characterize, for the first time, an experimental mouse model fed a high-fat diet (HFD) with a specific deletion of Adam17 in endothelial cells and to analyse the effects on different renal structures. Endothelial Adam17 knockout male mice and their controls were fed a high-fat diet, to induce obesity, or standard rodent chow, for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, macrophage infiltration, and galectin-3 levels were evaluated. Results showed that obese mice presented higher blood glucose levels, dysregulated glucose homeostasis, and higher body weight compared to control mice. In addition, obese wild-type mice presented an increased albumin-to-creatinine ratio; greater glomerular size and mesangial matrix expansion; and tubular fibrosis with increased galectin-3 expression. Adam17 deletion decreased the albumin-to-creatinine ratio, glomerular mesangial index, and tubular galectin-3 expression. Moreover, macrophage infiltration in the glomeruli of obese Adam17 knockout mice was reduced as compared to obese wild-type mice. In conclusion, the expression of ADAM17 in endothelial cells impacted renal inflammation, modulating the renal function and histology in an obese pre-diabetic mouse model.

Modern methods of influence at endometrial receptivity in patients with recurrent implantation failure (review)

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (3) ◽  
pp. 66-70
Author(s):  
M I Polovneva ◽  
I E Korneeva ◽  
O V Bourmenskaya
Keyword(s):  
Mononuclear Cells ◽  
Platelet Rich Plasma ◽  
Test System ◽  
Endometrial Receptivity ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Peripheral Blood Mononuclear ◽  
Repeated Implantation Failure ◽  
Endometrial Scratching ◽  
Modern Methods

Objective. To carry out an analysis of the data available in scientific literature on modern methods of influence at endometrial receptivity in patients with recurrent implantation failure. Materials and methods. The review includes the data of foreign and Russia papers published on PubMed during the last 7-10 years. Results. There are studies described the role of endometrial scratching, infusion granulocyte colony stimulating factor, autologous peripheral blood mononuclear cells, autologous platelet-rich plasma, the endometrial receptivity array in treatment for patients with repeated implantation failure. Conclusion. Several adjuvant therapies and diagnostic tests have been used along with IVF to increase the pregnancy rates for women with repeated implantation failure. Perhaps a new test-system to find personal predictors of endometrial receptivity can tern up a positive effect at patients with RIF.

scholarly journals Both Virus and Tumor Necrosis Factor Alpha Are Critical for Endothelium Damage in a Mouse Model of Dengue Virus-Induced Hemorrhage

2007 ◽  
Vol 81 (11) ◽  
pp. 5518-5526 ◽  
Author(s):  
Hsuen-Chin Chen ◽  
Florence M. Hofman ◽  
John T. Kung ◽  
Yang-Ding Lin ◽  
Betty A. Wu-Hsieh
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Mouse Model ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Endothelium Damage ◽  
Necrosis Factor

ABSTRACT Hemorrhage is a common clinical manifestation in dengue patients. However, the pathogenic mechanism of dengue virus (DV)-induced hemorrhage awaits clarification. We established a mouse model of DV hemorrhage using immunocompetent C57BL/6 mice by injecting DV serotype 2 strain 16681 intradermally. While inoculation of 3 × 109 PFU of DV induced systemic hemorrhage in all of the mice by day 3 of infection, one out of three of those injected with 4 × 107 to 8 × 107 PFU developed hemorrhage in the subcutaneous tissues. The mice that were inoculated with 4 × 107 to 8 × 107 PFU but that did not develop hemorrhage were used as a basis for comparison to explore the pathogenic mechanism of dengue hemorrhage. The results showed that mice with severe thrombocytopenia manifested signs of vascular leakage and hemorrhage. We observed that high viral titer, macrophage infiltration, and tumor necrosis factor alpha (TNF-α) production in the local tissues are three important events that lead to hemorrhage. Immunofluorescence staining revealed that DV targeted both endothelial cells and macrophages. In addition, the production of high levels of TNF-α in tissues correlated with endothelial cell apoptosis and hemorrhage. By comparing TNF-α−/− to IgH−/−, C5−/−, and wild-type mice, we found that TNF-α was important for the development of hemorrhage. In vitro studies showed that mouse primary microvascular endothelial cells were susceptible to DV but that TNF-α enhanced DV-induced apoptosis. Our mouse model illustrated that intradermal inoculation of high titers of DV predisposes endothelial cells to be susceptible to TNF-α-induced cell death, which leads to endothelium damage and hemorrhage development. This finding highlights the contribution of the innate immune response to dengue hemorrhage.

Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1810-1817 ◽  
Author(s):  
Annemie Collen ◽  
Roeland Hanemaaijer ◽  
Florea Lupu ◽  
Paul H. A. Quax ◽  
Natascha van Lent ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Collagen Matrix ◽  
Tubular Structures ◽  
Tubule Formation ◽  
Tnf Α ◽  
Membrane Type

Adult angiogenesis, associated with pathologic conditions, is often accompanied by the formation of a fibrinous exudate. This temporary matrix consists mainly of fibrin but is intermingled with plasma proteins and collagen fibers. The formation of capillary structures in a fibrinous matrix in vivo was mimicked by an in vitro model, in which human microvascular endothelial cells (hMVECs) seeded on top of a fibrin-10% collagen matrix form capillarylike tubular structures after stimulation with basic fibroblast growth factor/tumor necrosis factor α (bFGF/TNF-α) or vascular endothelial growth factor (VEGF)/TNF-α. In the fibrin-collagen matrix the metalloproteinase inhibitor BB94 inhibited tubule formation by 70% to 80%. Simultaneous inhibition of plasmin and metalloproteinases by aprotinin and BB94 caused a nearly complete inhibition of tubule formation. Adenoviral transduction of tissue inhibitor of metalloproteinases 1 (TIMP-1) and TIMP-3 into endothelial cells revealed that TIMP-3 markedly inhibited angiogenesis, whereas TIMP-1 had only a minor effect. Immunohistochemical analysis showed the presence of matrix metalloproteinase 1 (MMP-1), MMP-2, and membrane-type 1 (MT1)–MMP, whereas MMP-9 was absent. The endothelial production of these MMPs was confirmed by antigen assays and real-time polymerase chain reaction (PCR). MT1-MMP mRNA was markedly increased in endothelial cells under conditions that induced tubular structures. The presence of MMP-1, MMP-2, and MT1-MMP was also demonstrated in vivo in the newly formed vessels of a recanalized arterial mural thrombus. These data suggest that MMPs, in particular MT-MMPs, play a pivotal role in the formation of capillarylike tubular structures in a collagen-containing fibrin matrix in vitro and may be involved in angiogenesis in a fibrinous exudate in vivo.

scholarly journals Membrane type 1–matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 3956-3964 ◽  
Author(s):  
Salomón Matías-Román ◽  
Beatriz G. Gálvez ◽  
Laura Genís ◽  
María Yáñez-Mó ◽  
Gonzalo de la Rosa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Human Monocytes ◽  
Tumor Cell Migration ◽  
Monocyte Migration ◽  
Tnf Α ◽  
Membrane Type

Abstract Membrane type 1–matrix metalloproteinase (MT1-MMP) is involved in endothelial and tumor-cell migration, but its putative role in leukocyte migration has not been characterized yet. Here, we demonstrate that anti–MT1-MMP monoclonal antibody (mAb) impaired monocyte chemotactic protein-1 (MCP-1)–stimulated monocyte migration on fibronectin (FN), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). In addition, monocyte transmigration through tumor necrosis factor-α (TNF-α)–activated endothelium is also inhibited by anti–MT1-MMP mAb. Therefore, regulation of MT1-MMP in human peripheral blood monocytes was investigated. First, MT1-MMP clustering was observed at motility-associated membrane protrusions of MCP-1–stimulated monocytes migrating on FN, VCAM-1, or ICAM-1 and at the leading edge, together with profilin, of monocytes transmigrating through activated endothelial cells. In addition, up-regulation of MT1-MMP expression was induced in human monocytes upon attachment to FN in a manner dependent on α4β1 and α5β1 integrins. Binding of monocytes to TNF-α–activated human endothelial cells as well as to VCAM-1 or ICAM-1 also resulted in an increase of MT1-MMP expression. These findings correlated with an enhancement of MT1-MMP fibrinolytic activity in monocytes bound to FN, VCAM-1, or ICAM-1. Our data show that MT1-MMP is required during human monocyte migration and endothelial transmigration and that MT1-MMP localization, expression, and activity are regulated in monocytes upon contact with FN or endothelial ligands, pointing to a key role of MT1-MMP in monocyte recruitment during inflammation.

scholarly journals Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action

Reproduction ◽  
2015 ◽  
Vol 149 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Y Gnainsky ◽  
I Granot ◽  
P Aldo ◽  
A Barash ◽  
Y Or ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Endometrial Biopsy ◽  
Implantation Failure ◽  
Uterine Receptivity ◽  
Recurrent Implantation Failure ◽  
Endometrial Stromal Cells ◽  
Inflammatory Conditions ◽  
Adhesive Molecule ◽  
Inflammatory Milieu ◽  
Endometrial Epithelial Cells

A decade ago, we first reported that endometrial biopsy significantly improves the success of pregnancy in IVF patients with recurrent implantation failure, an observation that was later confirmed by others. Recently, we have demonstrated that this treatment elevated the levels of endometrial pro-inflammatory cytokines and increased the abundance of macrophages (Mac) and dendritic cells (DCs). We therefore hypothesised that the biopsy-related successful pregnancy is secondary to an inflammatory response, and aimed at deciphering its mechanism of action. Supporting our hypothesis, we found that the pro-inflammatory TNFα stimulated primary endometrial stromal cells to express cytokines that attracted monocytes and induced their differentiation into DCs. These monocyte-derived DCs stimulated endometrial epithelial cells to express the adhesive moleculeSPP1(osteopontin (OPN)) and its receptorsITGB3andCD44, whereasMUC16, which interferes with adhesion, was downregulated. Other implantation-associated genes, such asCHST2,CCL4(MIP1B) andGROA, were upregulated by monocyte-derived Mac. These findings suggest that uterine receptivity is mediated by the expression of molecules associated with inflammation. Such an inflammatory milieu is not generated in some IVF patients with recurrent implantation failure in the absence of local injury provoked by the biopsy treatment.

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