Gene expression changes induced in mouse bone marrow by placenta growth factor (PlGF) overexpression.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE52414 | GEO | 2021/11/01
REPOSITORIES: GEO
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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: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:PlGF expression profile in primary capillary PlGF-/- endothelial cells treated with 100 ng/ml PlGF during 6 hours.
2003-05-28 | E-MEXP-6 | biostudies-arrayexpress
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: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
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:HUVECs (human umbilical cord vein endothelial cells) are treated with the angiogenic factors VEGF-A (vascular endothelial growth factor-A) and PlGF (placental growth factor) in low or high serum media.
2007-09-27 | E-GEOD-837 | biostudies-arrayexpress
Project description:PGF (Placental growth factor) is a member of the vascular endothelial growth factor (VEGF) sub-family a crucial factor in angiogenesis and vasculogenesis. Mechanisms by which PlGF expression is regulated remain to be investigated in diabetic retinopathy DR. However, the underlying molecular mechanisms that PlGF, mediates in the early complications at non-proliferative DR remain mostly elusive. Here we have applied an LC-MS/MS-based label-free quantification proteomic approach to PlGF ablation in the retinal tissues from mouse strains (Akita, PlGF-/- and Akita.PlGF-/-). The proteomes of retinal tissues were extracted, digested by the Trypsin/LysC enzyme and subsequently analyzed by a Q-Exactive hybrid Quadrupole-Orbitrap mass spectrometer. We have performed normalization by the Z-score method, correlation by Pearson correlation coefficient and identified differentially expressed proteins in four comparisons. The gene ontology, functional pathways, and protein-protein network interaction analysis suggested that Gnb1, Gnb2, Gnb4, Gnai2, Gnao1, Snap2 and Gngt1 proteins are involved in insulin resistance pathways, which are down-regulated/ no significant in PlGF ablation in Akita diabetics (Akita.PlGF-/- vs. Akita), up-regulated in Akita vs. C57, PlGF-/- vs. C57. Prdx6, Map2 are involved in antioxidant activity and neural protection pathways respectively, which are up-regulated in Akita.PlGF-/- vs. Akita. Our proteomics outcomes anticipated that down-regulated of insulin resistance pathways, up-regulation of antioxidant and neuroprotection proteins might epitomize the potential mechanisms of anti-PlGF therapies in the treatment of DR.
2019-03-13 | PXD010757 | Pride
Project description:Background: Despite that vitamins or their derivatives (Vits), such as panthenyl ethyl ether, tocopherol acetate, or pyridoxine have been widely used in topical hair care products, their efficacy and mode of action have been insufficiently studied. Objective: To elucidate biological influence of Vits on hair follicles and dissect underlying mechanisms. Methods: Mouse vibrissa hair follicle organ culture model was utilized to evaluate the effects of Vits on hair shaft elongation. Gene and protein expression analyses, and histological investigation were conducted to elucidate responsible mechanisms. Human hair follicle cell culture was adopted to assess clinical relevance. Results: In organ culture models, the combination of panthenyl ethyl ether, tocopherol acetate, and pyridoxine (namely PPT) supplementation significantly promoted hair shaft elongation. PPT-treatment enhanced hair matrix cell proliferation by 1.9 folds compared to controls, as demonstrated by Ki-67 positive immunoreactivity. PPT-treated mouse dermal papillae up-regulated Placental growth factor (Plgf) by 1.6 folds, compared to non-treated controls. Importantly, addition of PlGF neutralizing antibodies to the ex vivo culture diminished the promotive effect on hair growth and the increase in VEGFR1 phosphorylation achieved by PPT. A VEGFR1 inhibitor also repressed the promotion of hair shaft elongation. Microarray analysis suggested synergistic summation of individual Vit bioactivity, putatively explaining the effect of PPT. Moreover, PPT increased PlGF secretion in cultured human dermal papilla cells. Conclusion: Our findings suggested that PPT promoted hair shaft elongation via activating PlGF/VEGFR-1 signaling. The current study can shed light on the previously underrepresented advantage of utilizing Vits for ameliorating hair care products.
2022-06-30 | GSE202865 | GEO
Project description:Gene expression changes induced in mouse bone marrow by placenta growth factor (PlGF) overexpression.
| PRJNA228193 | ENA