Genes induced by PDGF-BB in cells lacking Signal Transducer and Activator of Transcription-1 (Stat1)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE152342 | GEO | 2020/06/13
REPOSITORIES: GEO
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Project description:Genes induced by PDGF-BB in cells lacking Signal Transducer and Activator of Transcription-1 (Stat1)
| PRJNA639057 | ENA
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: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: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: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:Anti-PDGF agents are routinely used as a key component in front-line therapy for the treatment of various cancers. However, molecular mechanisms underlying their impact on vascular remodeling in relation to the dose issue remain poorly understood. Here we show that in high PDGF-BB-producing tumors, anti-PDGF drugs significantly inhibited tumor growth and metastasis by preventing pericyte (PC) loss and vascular permeability. Surprisingly, the same anti-PDGF-BB drugs promoted tumor cell dissemination and metastasis in PDGF-BB-low-producing or negative tumors by ablating PCs from tumor vessels. At the molecular level, we show that the PDGFR-β signaling pathway in PCs mediated the opposing effects and persistent exposure of PCs to PDGF-BB led to marked downregulation of PDGFR-β. Inactivation of the PDGFR-β signaling system led to decreased levels of integrin α1β1, resulted in impaired adhesion of PCs to collagen I, IV and laminin, two principal extracellular matrix components in blood vessels for interaction with these integrins. Our data suggest that tumor PDGF-BB levels may serve as an important biomarker for selection of tumor-bearing hosts for beneficial therapy and unsupervised practice of this group of drugs could potentially promote tumor invasion and metastasis.
2013-07-22 | GSE46564 | GEO
Project description:Anti-PDGF agents are routinely used as a key component in front-line therapy for the treatment of various cancers. However, molecular mechanisms underlying their impact on vascular remodeling in relation to the dose issue remain poorly understood. Here we show that in high PDGF-BB-producing tumors, anti-PDGF drugs significantly inhibited tumor growth and metastasis by preventing pericyte (PC) loss and vascular permeability. Surprisingly, the same anti-PDGF-BB drugs promoted tumor cell dissemination and metastasis in PDGF-BB-low-producing or negative tumors by ablating PCs from tumor vessels. At the molecular level, we show that the PDGFR-? signaling pathway in PCs mediated the opposing effects and persistent exposure of PCs to PDGF-BB led to marked downregulation of PDGFR-?. Inactivation of the PDGFR-? signaling system led to decreased levels of integrin ?1?1, resulted in impaired adhesion of PCs to collagen I, IV and laminin, two principal extracellular matrix components in blood vessels for interaction with these integrins. Our data suggest that tumor PDGF-BB levels may serve as an important biomarker for selection of tumor-bearing hosts for beneficial therapy and unsupervised practice of this group of drugs could potentially promote tumor invasion and metastasis. Pericytes were isolated and treated with PDGF-BB or control for 5 days.
2013-07-22 | E-GEOD-46564 | biostudies-arrayexpress
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:Atherosclerosis is the most important mechanism of cardiovascular and cerebrovascular diseases and has become one of the most serious diseases that threaten human health. Vascular smooth muscle cells (VSMCs) are the main cellular components that constitute the structure of the blood vessel wall. The excessive proliferation and migration are pivotal pathological basis of atherosclerosis, in-stent restenosis, pulmonary hypertension and other vascular proliferative diseases. PDGF-BB is a potent proliferative agent for VSMCs, but the specific mechanism of PDGF-BB signaling pathway involved in biological processes such as proliferation and migration of VSMCs is not elusive.
2023-10-22 | GSE186313 | 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