Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA139313 | ENA |
REPOSITORIES: ENA
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Project description:Numerous studies have suggested a link between fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling pathways; however the nature of this link has not been established. To evaluate this relationship we investigated VEGF signaling in endothelial cells with disrupted FGF signaling in vitro and in vivo. We find that endothelial cells lacking FGF signaling become unresponsive to VEGF due to down regulation of VEGFR2 expression caused by reduced Vegfr2 enhancer activation, which is in turn caused by reduced activation of Ets family transcription factors. In vivo this manifests in the loss of vascular integrity and morphogenesis. Thus, basal FGF stimulation of the endothelium is required for maintenance of VEGFR2 expression and the ability to respond to VEGF stimulation and accounts for the hierarchic control of vascular formation by FGFs and VEGF. Primary mouse lung endothelial cells were transduced with either Adeno-Null (empty) or Adeno- dominant negative FGF receptor 1 and harvested 24 hours after transduction. Total RNA was extracted and subjected to the analysis using SuperArray GEArray Q Series Mouse Angiogenesis Gene Array. Comparisons were made between treatments.
2011-06-07 | E-GEOD-28483 | biostudies-arrayexpress
Project description:We checked whether the inhibition of the FGF, VEGF, and TGF signaling pathways would influence the miRNA profile in ECs, co-cultured with NSPCs. EC/NSPC co-cultures were incubated with FGF/VEGF receptor inhibitor PD 173074 (1μM in DMSO), and the TGF-β receptor inhibitor SB431542 (10μM in DMSO, Millipore)
2012-01-01 | E-GEOD-32352 | biostudies-arrayexpress
Project description:Numerous studies have suggested a link between fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling pathways; however the nature of this link has not been established. To evaluate this relationship we investigated VEGF signaling in endothelial cells with disrupted FGF signaling in vitro and in vivo. We find that endothelial cells lacking FGF signaling become unresponsive to VEGF due to down regulation of VEGFR2 expression caused by reduced Vegfr2 enhancer activation, which is in turn caused by reduced activation of Ets family transcription factors. In vivo this manifests in the loss of vascular integrity and morphogenesis. Thus, basal FGF stimulation of the endothelium is required for maintenance of VEGFR2 expression and the ability to respond to VEGF stimulation and accounts for the hierarchic control of vascular formation by FGFs and VEGF.
2011-06-07 | GSE28483 | GEO
Project description:Lysosomal degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is emerging as a critical regulator of ER homeostasis and function1. The selective incorporation of ER fragments into nascent autophagosomes is facilitated by ER resident proteins, ER-phagy receptors, that bind the autophagosomal LC3 protein via the cytosolic LC3 interacting domain (LIR) (REF). However, the molecular mechanisms that regulate ER-phagy in response to cellular needs are still largely unknown. We found that the MiT/TFE transcription factors - master regulators of lysosomal biogenesis and autophagy2- control ER-phagy by inducing the expression of the ER-phagy receptor FAM134B. This pathway is robustly activated in chondrocytes by FGF signaling, a critical regulator of chondrocyte differentiation3. FGF triggers TFEB/TFE3-mediated ER-phagy through JNK-dependent proteasomal degradation of the insulin receptor substrate 1 (IRS-1) protein and inhibition of the insulin signaling. FAM134B knock-down impairs cartilage growth and mineralization in medaka fish, suggesting a physiological role for this process during skeletal growth. Notably, we showed that the TFEB/TFE3-FAM134B axis promotes ER-phagy activation upon prolonged starvation. Thus, this study identifies MiT/TFE-factors as key transcriptional activators of ER-phagy in response to both metabolic and developmental cues.
2020-07-15 | PXD015130 | Pride
Project description:Among the three embryonic germ layers, mesoderm plays a central role in the establishment of the vertebrate body plan. Mesoderm is specified by secreted signaling proteins from the FGF, Nodal, BMP and Wnt families. No new classes of extracellular mesoderm-inducing factors have been identified in more than two decades. Here we show that the Xenopus pinhead (pnhd) gene encodes a novel secreted protein that activates specific mesodermal markers in presumptive ectoderm. We demonstrate that Pnhd is required for the specification of a subset of embryonic mesoderm in vivo. RNA sequencing revealed that many transcriptional targets of Pnhd are shared with those of the FGF pathway. Pnhd signaling involves active FGF but not Wnt receptors and is accompanied by Erk1 phosphorylation. We propose that Pnhd operates in the marginal zone to specify mesodermal progenitors via an FGF receptor-dependent mechanism.
2020-05-15 | GSE143795 | GEO
Project description:Lysosomal degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is emerging as a critical regulator of cell homeostasis and function1. The recent identification of ER-phagy receptors has shed light on the molecular mechanism underlining this process; however, the signaling pathways regulating ER-phagy in response to cellular needs are still largely unknown. We found that the nutrient responsive transcription factors TFEB and TFE3 - master regulators of lysosomal biogenesis and autophagy2- control ER-phagy by inducing the expression of the ER-phagy receptor FAM134B. The TFEB/TFE3-FAM134B axis promotes ER-phagy activation upon prolonged starvation. In addition, we discovered that this pathway is activated in chondrocytes by FGF signaling, a critical regulator of cell differentiation 3. FGF signaling induces a JNK-dependent proteasomal degradation of the insulin receptor substrate 1, which inhibits the insulin-PI3K-PKB/Akt-mTORC1 pathway and promotes TFEB/TFE3 nuclear translocation and FAM134B induction. Consistent with a role of the TFEB/TFE3-FAM134B axis in chondrocytes, FAM134B knock-down impairs cartilage growth and mineralization in medaka fish. This study identifies a new signaling pathway that allows ER-phagy to respond to both metabolic and developmental cues.
2020-07-15 | PXD015326 | Pride
Project description:Vascular endothelial growth factor (VEGF) signaling serves a central role in vascular development as well as maintaining vascular homeostasis. In endothelial cells (ECs), VEGF activates gene expression of angiogenic transcription factors (TFs) followed by downstream induction of angiogenic responsive genes. Recent findings support histone modification dynamics contribute to transcriptional control of genes important for EC functions. Lysine demethylase 2B (KDM2B) demethylates histone H3K4me3 and H3K36me2/3 and also mediates monoubiquitylation of histone H2A119K. KDM2B functions as a transcriptional repressor in somatic cell reprograming and tumor development. However, the role of KDM2B during VEGF-signaling remains to be elucidated. Here, we show in cultured human ECs that knockdown of KDM2B enhances VEGF-induced angiogenesis via increased abilities of migration and proliferation. In contrast, ectopic expression of KDM2B has inhibitory effects on angiogenesis. The function of KDM2B is possibly dependent on its catalytic Jumondi C domain. Genome-wide analysis further reveal that KDM2B selectively controls transcription of VEGF-induced angiogenic TFs where increased H3K4me3/H3K36me3 and decreased of H2A119Kub are associated. These findings suggest an essential role of KDM2B during VEGF-signaling in ECs. Because dysregulation of VEGF signaling in ECs is involved in various diseases including cancer, KDM2B may be a potential therapeutic target in VEGF-mediated vasculopathic diseases.
2022-04-01 | GSE196505 | GEO
Project description:Vascular endothelial growth factor (VEGF) signaling serves a central role in vascular development as well as maintaining vascular homeostasis. In endothelial cells (ECs), VEGF activates gene expression of angiogenic transcription factors (TFs) followed by downstream induction of angiogenic responsive genes. Recent findings support histone modification dynamics contribute to transcriptional control of genes important for EC functions. Lysine demethylase 2B (KDM2B) demethylates histone H3K4me3 and H3K36me2/3 and also mediates monoubiquitylation of histone H2A119K. KDM2B functions as a transcriptional repressor in somatic cell reprograming and tumor development. However, the role of KDM2B during VEGF-signaling remains to be elucidated. Here, we show in cultured human ECs that knockdown of KDM2B enhances VEGF-induced angiogenesis via increased abilities of migration and proliferation. In contrast, ectopic expression of KDM2B has inhibitory effects on angiogenesis. The function of KDM2B is possibly dependent on its catalytic Jumondi C domain. Genome-wide analysis further reveal that KDM2B selectively controls transcription of VEGF-induced angiogenic TFs where increased H3K4me3/H3K36me3 and decreased of H2A119Kub are associated. These findings suggest an essential role of KDM2B during VEGF-signaling in ECs. Because dysregulation of VEGF signaling in ECs is involved in various diseases including cancer, KDM2B may be a potential therapeutic target in VEGF-mediated vasculopathic diseases.
2022-04-01 | GSE196503 | GEO
Project description:Its known that FGF signaling induces pigment cell precursors formation. We perturbed the endogenous FGF signaling cascade by using a dominant-negative form of the unique Ci-FGF receptor (FGFRDN) and a constitutively active form of Ci-Ets1/2 (Ets:Vp16), a transcriptional effector of FGF/MAP Kinase cascade. Targeted expression of dominant negative FGF receptor and Ets:VP16 fusion protein was achieved in PCPs using the Tyrosinase-related protein 1/2a (Tyrp1/2a) cis-regulatory region. The PCPs were isolated by Fluorescent Activated Cell Sorting (FACS) as GFP+ cells at two developmental stages: 8 hpf at ~16C (neurula stage) corresponding to early FGF-mediated induction and 12 hpf at ~18C (tailbud stage) where PCPs are already fate restricted as pigment cells. To avoid a contamination by mesenchyme cells where Ciona enhancers are often ectopically activated, we co-electroporated the MyoD905>YFP construct and counter-selected YFP+ cells. In summary the conditions used are: FGFRDN, Ets:VP16 and Control samples at 8 and 12 hpf (four samples for each condition).
2014-07-14 | E-MTAB-2759 | biostudies-arrayexpress
Project description:The project concerns vascular endothelial growth factor (VEGF) signaling, which is dependent on binding of VEGF to VEGF receptor-2 (VEGFR2) and leads to activation of the receptor kinase and autophosphorylation. Previous mouse studies with the VEGFR-2 phosphorylation site mutation Y1212F showed reduced vascular stability. We here investigate with LC-MS proteomics which signal transduction pathway(s) are lost in the mutant by identifying proteins that bind to the Y1212F site.
2019-08-13 | PXD014517 | Pride