Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA228193 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor family and plays an important role in adult pathological angiogenesis. To further investigate PlGF functions in tumor growth and metastasis formation, we used transgenic mice overexpressing PlGF. Recent studies demonstrate that tumor vascularization does not exclusively rely on preexisting vessels but also depends on bone marrow derived progenitor cells. The aim of the present work is to investigate the effect of the PlGF overexpression in the skin on the transcriptional landscape of bone marrow derived cells.
2021-11-01 | GSE52414 | GEO
Project description:T-helper (Th) cells actively communicate with adjacent cells by secreting soluble mediators, and yet crosstalk between Th cells and endothelial cells is poorly understood. Placental growth factor (PlGF), originally identified in the placenta, is an angiogenic factor homologous to vascular endothelial growth factor (VEGF)-A. We performed transcriptome analysis to systemically compare the effect of IL6, a key factor in Th cell polarization, and PlGF on T cell functions.
2019-06-14 | GSE118281 | GEO
Project description:The placental growth factor (PlGF) is member of the vascular endothelial growth factor (VEGF)-family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages and bone marrow progenitor cells and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in the pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile. In this study, we assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF-knock out mice and monoclonal antibodies targeting PlGF in an orthotopic model for HCC. In addition, the effect of PlGF-antibodies is compared to that of Sorafenib, as well as the combination of both therapies. In our study we have found that both in a transgenic knock out model as in a treatment model, silencing or inhibition of PlGF significantly decreased tumour burden, not only by inhibiting the vascularisation, but also by decreasing hepatic macrophage recruitment and by normalizing the remaining blood vessels, thereby decreasing hypoxia and thus, reducing the pro-metastatic potential of HCC. Conclusion: considering its favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, targeting PlGF could become a valuable therapeutic strategy against HCC.
2014-12-23 | GSE35289 | GEO
Project description:The placental growth factor (PlGF) is member of the vascular endothelial growth factor (VEGF)-family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages and bone marrow progenitor cells and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in the pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile. In this study, we assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF-knock out mice and monoclonal antibodies targeting PlGF in an orthotopic model for HCC. In addition, the effect of PlGF-antibodies is compared to that of Sorafenib, as well as the combination of both therapies. In our study we have found that both in a transgenic knock out model as in a treatment model, silencing or inhibition of PlGF significantly decreased tumour burden, not only by inhibiting the vascularisation, but also by decreasing hepatic macrophage recruitment and by normalizing the remaining blood vessels, thereby decreasing hypoxia and thus, reducing the pro-metastatic potential of HCC. Conclusion: considering its favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, targeting PlGF could become a valuable therapeutic strategy against HCC. Hybridisation on the Mouse Gene Expression Microarray (Agilent) was performed in a single sample per chip and in a monocolore mode, using cyanine-3 (Cy3) labeling. Following conditions were assessed: 25W DEN + 5W αPlGF tumour tissue (n = 5), 25W DEN + 5W αPlGF surrounding tissue (n = 4), 25W DEN + 5W IgG tumour tissue (n = 5), 25W DEN + 5W IgG surrounding tissue (n = 4), 25W saline + 5W αPlGF (n = 3) and 25W saline + 5W IgG (n = 3).
2014-12-23 | E-GEOD-35289 | biostudies-arrayexpress
Project description:Inflammation-mediated oncogenesis has been implicated in a variety of cancer types. Rheumatoid synovial tissues can be viewed as a tumor-like mass, consisting of hyperplastic fibroblast-like synoviocytes (FLSs). FLSs of rheumatoid arthritis (RA) patients have pro-migratory and invasive characteristics, which may be caused by chronic exposure to genotoxic stimuli, including hypoxia and growth factors. We tested whether a transformed phenotype of RA-FLSs is associated with placental growth factor (PlGF), a representative angiogenic growth factor induced by hypoxia. Here, we identified PlGF-1 and PlGF-2 as the major PlGF isoforms in RA-FLSs. Global gene expression profiling revealed that cell proliferation, apoptosis, angiogenesis, and cell migration were mainly represented by differentially expressed genes in RA-FLSs transfected with siRNA for PlGF. Indeed, PlGF-deficient RA-FLSs showed a decrease in cell proliferation, migration, and invasion, but an increase in apoptotic death in vitro. PlGF gene overexpression resulted in the opposite effects. Moreover, exogeneous PlGF-1 and PlGF-2 increased survival, migration, and invasiveness of RA-FLSs by binding their receptors, Flt-1 and NP-1, up-regulating the expression of anti-apoptotic molecules, pErk and Bcl2. Knock-down of PlGF transcripts reduced RA-FLS proliferation in a xeno-transplantation model. Collectively, in addition to their role for neovascularization, PlGF-1 and -2 promote proliferation, survival, migration, and invasion of RA-FLSs in an autocrine and paracrine manner. These results demonstrated how primary cells of mesenchymal origin acquired an aggressive and transformed phenotype. PlGF and its receptors thus offer new targets for anti-FLS therapy. The FLSs were prepared from the synovial tissues of RA patients and incubated in DMEM supplemented with 10% FBS. Cells were cultured in RPMI supplemented with 10% FBS. There are 4 FLS samples treated with PlGF siRNA, and 4 FLS samples treated with control siRNA.
2015-01-14 | E-GEOD-64922 | biostudies-arrayexpress
Project description:Angiogenesis induced by placental growth factor (PlGF) in heart promotes myocardial hypertrophy through the paracrine action of endothelium-derived nitric oxide which triggers the degradation of RGS4 and subsequent the activation of Akt/mTORC1 pathway in cardiomyocytes. However, whether alterations in miRNAs contribute to the development of hypertrophy is largely undetermined. We found that miR-182 contributed to the hypertrophic response and activation of Akt/mTORC1 pathway by suppressing the expression of Bcat2, Pink1, Adcy6, Foxo3. miR-182 targeted genes were investigated in the mouse model of myocardial angiogenesis induced by conditional, cardiac specific expression of PlGF. We also induced angiogenesis, but blocked hypertrophy by concomitant expression of PlGF and RGS4 (PlGF/RGS4 mice). The mRNA expression profiling in PlGF and PlGF/RGS4 mice were assessed after 6 weeks of transgene expression, concurent with the development of myocardial hypertrophy.
2016-02-17 | E-GEOD-67815 | biostudies-arrayexpress
Project description:Inflammation-mediated oncogenesis has been implicated in a variety of cancer types. Rheumatoid synovial tissues can be viewed as a tumor-like mass, consisting of hyperplastic fibroblast-like synoviocytes (FLSs). FLSs of rheumatoid arthritis (RA) patients have pro-migratory and invasive characteristics, which may be caused by chronic exposure to genotoxic stimuli, including hypoxia and growth factors. We tested whether a transformed phenotype of RA-FLSs is associated with placental growth factor (PlGF), a representative angiogenic growth factor induced by hypoxia. Here, we identified PlGF-1 and PlGF-2 as the major PlGF isoforms in RA-FLSs. Global gene expression profiling revealed that cell proliferation, apoptosis, angiogenesis, and cell migration were mainly represented by differentially expressed genes in RA-FLSs transfected with siRNA for PlGF. Indeed, PlGF-deficient RA-FLSs showed a decrease in cell proliferation, migration, and invasion, but an increase in apoptotic death in vitro. PlGF gene overexpression resulted in the opposite effects. Moreover, exogeneous PlGF-1 and PlGF-2 increased survival, migration, and invasiveness of RA-FLSs by binding their receptors, Flt-1 and NP-1, up-regulating the expression of anti-apoptotic molecules, pErk and Bcl2. Knock-down of PlGF transcripts reduced RA-FLS proliferation in a xeno-transplantation model. Collectively, in addition to their role for neovascularization, PlGF-1 and -2 promote proliferation, survival, migration, and invasion of RA-FLSs in an autocrine and paracrine manner. These results demonstrated how primary cells of mesenchymal origin acquired an aggressive and transformed phenotype. PlGF and its receptors thus offer new targets for anti-FLS therapy.
2015-01-14 | GSE64922 | GEO
Project description:Angiogenesis induced by placental growth factor (PlGF) in heart promotes myocardial hypertrophy through the paracrine action of endothelium-derived nitric oxide which triggers the degradation of RGS4 and subsequent activation of the Akt/mTORC1 pathway in cardiomyocytes. However, whether alterations in miRNAs contribute to the development of hypertrophy is largely undetermined. We found that miR-182 contributed to the hypertrophic response and activation of the Akt/mTORC1 pathway by suppressing the expression of Bcat2, Pink1, Adcy6, Foxo3. The expression of miRNAs and the effects of anti-miRs were investigated in the mouse model of myocardial angiogenesis induced by conditional, cardiac specific expression of PlGF. We also induced angiogenesis, but blocked hypertrophy by concomitant expression of PlGF and RGS4 (PlGF/RGS4 mice). Microarray profiling of miRNAs in LV myocardium was determined after 3 and 6 weeks of transgene expression.
2016-02-17 | E-GEOD-67814 | biostudies-arrayexpress
Project description:Gene expression changes induced by overexpression of IDH1mut in the sorted mouse bone marrow cells
| PRJNA192836 | ENA
Project description:High levels of placental growth factor (PlGF) are pathological, however its function in endometrial cells remains to be investigated. Cell proliferation and motility requires actin reorganization, which is under the control of various signalling pathways including Rac1 and PAK1 proteins. In this study, we explored whether PlGF induces change in endometrial mechanics by modifying actin cytoskeleton thus contributing to cell stiffness at the maternal interface. To this end, human endometrial stromal cells (EnSCs) were treated with 20 ng/mL for 6 days with PlGF and its influence on cellular mechanics was investigated with atomic force microscopy (AFM), electrical impedance spectroscopy and proteomics methods. Proteomic analysis shows PlGF upregulated RhoGTPases activating proteins and extracellular matrix organization associated proteins. Rac1 and PAK1 transcript levels, activity and actin polymerization were significantly increased with in vitro PlGF treatment. AFM further revealed an increase in cell stiffness with PlGF. The PlGF effect on actin polymerization was inhibited with siRNA- Rac1, PAK1 and WAVE2. PlGF induced cell stiffness was pharmacologically reversed with pravastatin, resulting in improved trophoblast cell invasion as measured using electrical impedance spectroscopy. Thus, PlGF treatment leads to enhanced Rac1 and PAK1 levels, leading to an increase in cell stiffness, impairing trophoblast invasion. Taken together, aberrant PlGF levels can contribute to an altered pre-pregnancy maternal microenvironment and offers a coherent and unifying explanation for the pathological changes observed in pre-eclampsia (PE) conditions.
2024-06-23 | PXD050237 | Pride