Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA111211 | ENA |
REPOSITORIES: ENA
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Project description:We analyzed gene expression in human fibroblasts stimulated by platelet-derived growth factor-BB (PDGF-BB) or basic fibroblast growth factor (bFGF) for 1h and 24h. The results of two independent experiments were merged. SAM analysis identified 116 relevant probe sets. Hierarchical clustering of these probe sets showed divergent early gene regulation by PDGF and FGF but overlapping late response. We first analyzed genes commonly regulated by PDGF-BB and b-FGF more than 2 fold after 24h of stimulation and we found that these two growth factors repressed FOXO. We then focused on the early gene expression response induced by both growth factors. We performed a fold change analysis and found 114 probe sets regulated by PDGF-BB and 42 probe sets regulated by b-FGF, 37 of which were shared between the two gene lists . Keywords: Time course, cell Treatment comparison
2009-03-16 | GSE14256 | GEO
Project description:We analyzed gene expression in human fibroblasts stimulated by platelet-derived growth factor-BB (PDGF-BB) or basic fibroblast growth factor (bFGF) for 1h and 24h. The results of two independent experiments were merged. SAM analysis identified 116 relevant probe sets. Hierarchical clustering of these probe sets showed divergent early gene regulation by PDGF and FGF but overlapping late response. We first analyzed genes commonly regulated by PDGF-BB and b-FGF more than 2 fold after 24h of stimulation and we found that these two growth factors activated SREBP and E2F and repressed FOXO. We then focused on the early gene expression response induced by both growth factors. We performed a fold change analysis and found 114 probe sets regulated by PDGF-BB and 42 probe sets regulated by b-FGF, 37 of which were shared between the two gene lists . We found by data mining that both PDGF-BB and b-FGF activated AP-1 and NF-kB. Next we analyzed genes specifically regulated by PDGF-BB and found that STATs are specifically activated by PDGF and not by FGF. Experiment Overall Design: Human foreskin fibroblasts (AG01518) were cultured (1.5E6 cells/10 cm dish) in MEM medium with 10% fetal calf serum and glutamine for 24h, then washed and incubated for 47h in serum-free medium. Cells were stimulated for 1h by PDGF-BB (25ng/ml) or b-FGF (10ng/ml, + heparine 50 microg/ml). Alternatively, cells were incubated for 24h in starvation medium and treated for 24h with growth factors, or left untreated for 48h in serum-free medium (control treatment). Experiment Overall Design: Two biological replicates were performed
2009-03-20 | E-GEOD-14256 | biostudies-arrayexpress
Project description:The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. Comparison of S17 stromal cells treated with PDGF-BB for 72h to control
2011-12-04 | E-GEOD-33717 | biostudies-arrayexpress
Project description:The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis.
2011-12-04 | GSE33717 | GEO
Project description:Vascular pericytes, an important cellular component, in the tumor microenvironment, are often associated with tumor vasculatures and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte fibroblast transition (designated as PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that the PDGF-BB-PDGFRβ signaling promotes PFT in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, i.e., TN-AP-CreERT2:R26R-tdTomato and NG2:R26R-tdTomato, shows that PFT cells gains stromal fibroblast and myofibroblast markers in tumors. Importantly, co-implantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells (CTCs) and metastasis. Our findings reveal a novel mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT and thus targeting PFT may offer a new treatment option of cancer metastasis. Pericytes were isolated and treated with PDGF-BB or control for 1 or 5 days
2016-08-24 | E-GEOD-85955 | biostudies-arrayexpress
Project description:Vascular pericytes, an important cellular component, in the tumor microenvironment, are often associated with tumor vasculatures and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte fibroblast transition (designated as PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that the PDGF-BB-PDGFRβ signaling promotes PFT in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, i.e., TN-AP-CreERT2:R26R-tdTomato and NG2:R26R-tdTomato, shows that PFT cells gains stromal fibroblast and myofibroblast markers in tumors. Importantly, co-implantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells (CTCs) and metastasis. Our findings reveal a novel mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT and thus targeting PFT may offer a new treatment option of cancer metastasis.
2016-08-24 | GSE85955 | GEO
Project description:PDGF-BB:PDGFRβ signalling in brain pericytes is critical to the development, maintenance and function of a healthy blood-brain barrier (BBB). Furthermore, BBB impairment and pericyte loss in Alzheimer’s disease (AD) is well documented. We used tissue microarrays from control and AD brains to determine if PDGF-BB:PDGFRβ signalling components were altered in AD, and found that there was a reduction in vascular expression of PDGFB. We hypothesised that reduced PDGF-BB:PDGFRβ signalling in pericytes may have an impact on functions related to the BBB. We therefore tested the effects of PDGF-BB on primary human brain pericytes in vitro to define important signalling pathways and outcomes related to BBB function. Pericytes demonstrate a biphasic response to PDGF-BB, predominantly dependent on Akt and ERK. We determined that the actions of PDGF-BB are on-target at PDGFRβ, leading to internalisation and degradation of PDGFRβ. Using pharmacological inhibitors, we dissected distinct aspects of the PDGF-BB response that are controlled by ERK and Akt pathways. PDGF-BB promotes the proliferation of pericytes and protection from toxic stimuli through ERK signalling. In contrast, PDGF-BB:PDGFRβ signalling through Akt and NF-κB augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB or small molecule agonists to stabilise the cerebrovasculature in AD.
2021-11-30 | GSE189712 | GEO
Project description:Mesenchymal stem cells (MSCs) are multipotent stem cells that are under investigation for use in clinical trials because they are capable of self-renewal and differentiating into different cell types under defined conditions. Nonetheless, the therapeutic effects of MSCs have been constrained by low engraftment rates, cell fusion, and cell survival. Various strategies have been explored to improve the therapeutic efficacy of MSCs, with platelet-derived growth factor (PDGF)-BB emerging as a promising candidate. To enhance our comprehension of the impact of PDGF-BB on the gene expression profile and chromosomal accessibility of MSCs, RNA-sequencing and analysis of chromatin accessibility profiles were conducted on three human primary MSCs in culture, both with and without stimulation by PDGF-BB. Integrative analysis of gene expression and chromatin accessibility demonstrated that PDGF-BB treatment modified the chromatin accessibility landscape, marking regions for activation or repression through the AP-1 family transcription factors TEAD, CEBP, and RUNX2. These changes in AP1 transcription factor expression, in turn, led to cell proliferation and differentiation potential towards osteoblasts, adipocytes, or chondrocytes. The degree of MSC differentiation varies among cells isolated from different donors. The presence of an enrichment of exosome-related genes is also noted among all the differentially expressed genes. In conclusion, the observed changes in AP1 transcription factor expression not only induced cellular proliferation and differentiation, but also revealed variations in the degree of MSC differentiation based on donor-specific differences. Moreover, the enrichment of exosome-related genes among differentially expressed genes suggests a potential significant role for PDGF-BB in facilitating intercellular communication.
2024-10-01 | GSE272136 | GEO
Project description:To explore global molecular changes in smooth muscle in response to PDGFR activation, primary human bladder smooth muscle cells were treated with 1 nM PDGF-BB (hereafter PDGF) for 0, 4 or 24 h. Total RNA were prepared, and analyzed using expression profiling, and subjected to bioinformatic and functional interrogation. To identify molecular signatures of bladder smooth muscle peturbed by PDGF, primary human bladder smooth muscle cells were treated with 1 nM PDGF-BB (hereafter PDGF) for 0, 4 or 24 h.
2014-10-06 | E-GEOD-52488 | biostudies-arrayexpress