Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA189473 | ENA |
REPOSITORIES: ENA
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Project description:While therapeutic angiogenesis holds promise for vascular diseases, progress has been limited due to discrepancies in defining adult endothelial progenitors. We have identified and characterized a population of pluripotent derived NRP1+CD34+ nascent endothelial cells, immediately diverged from NRP1+CD34- mesodermal cells. We contrasted the transcriptional profile of NRP1+ CD34+ nascent endothelial cells against undifferentiated human pluripotent stem cells and human umbilical vein endothelial cells (HUVECs) to gain insights into the pathways that are uniquely activated in formation of new endothelium. We found significant upregulation of IL-6 related growth factor receptors, including ciliary neurotrophic factor receptor (CNTFR), and their downstream JAK/STAT signaling components in NRP1+CD34+ endothelial cells. When exposed to CNTF, angiogenic sprouting of NRP1+CD34+ was induced in Matrigel, which was abolished with JAK2 inhibition. Furthermore, we found evidence of JAK2 dependent cytokine signaling in more mature endothelium, highlighting the significance of the IL6R/JAK2 pathway, well known in hematopoiesis, in vascular biology. The findings identify a novel group of growth factor receptors and downstream signaling components that may be targeted to modulate angiogenesis and vasculogenesis. 7 samples analyzed, 2 replicates for NRP1+CD34+, 3 replicates for NRP1+CD34-
2013-12-14 | E-GEOD-44328 | biostudies-arrayexpress
Project description:While therapeutic angiogenesis holds promise for vascular diseases, progress has been limited due to discrepancies in defining adult endothelial progenitors. We have identified and characterized a population of pluripotent derived NRP1+CD34+ nascent endothelial cells, immediately diverged from NRP1+CD34- mesodermal cells. We contrasted the transcriptional profile of NRP1+ CD34+ nascent endothelial cells against undifferentiated human pluripotent stem cells and human umbilical vein endothelial cells (HUVECs) to gain insights into the pathways that are uniquely activated in formation of new endothelium. We found significant upregulation of IL-6 related growth factor receptors, including ciliary neurotrophic factor receptor (CNTFR), and their downstream JAK/STAT signaling components in NRP1+CD34+ endothelial cells. When exposed to CNTF, angiogenic sprouting of NRP1+CD34+ was induced in Matrigel, which was abolished with JAK2 inhibition. Furthermore, we found evidence of JAK2 dependent cytokine signaling in more mature endothelium, highlighting the significance of the IL6R/JAK2 pathway, well known in hematopoiesis, in vascular biology. The findings identify a novel group of growth factor receptors and downstream signaling components that may be targeted to modulate angiogenesis and vasculogenesis.
2013-12-14 | GSE44328 | GEO
Project description:Mitochondrial DNA-depleted human skin fibroblasts (HSF rho0) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-kappaB and STAT3 signaling pathways and by decreased activity of the mitochondrial death pathway, compared to the parent rho+ HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor-mediated death pathway remained highly active, and exogenous TRAIL induced higher levels of apoptosis in rho0 cells compared to rho+ HSF. Global gene expression analysis using microarray and quantitative RT-PCR demonstrated that expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, IGFL2), cytokines (IL6, IL17B, IL18, IL19, IL28B) and cytokine receptors (IL1R1, IL21R, IL31RA) were substantially decreased after mitochondrial depletion. Some of these genes were targets of NF-kappaB and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation induced expression of several NF-kappaB/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in rho+ HSF, but this response was substantially decreased in rho0 HSF. Suppression of the IKK-NF-kappaB pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated rho+ HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in rho+ HSF. However, NF-kappaB activation was partially lost in mitochondrial DNA-depleted HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-kappaB targets, further suppressing IL6-JAK2-STAT3, that in concert with NF-kappaB, regulated protection against TRAIL-induced apoptosis. There are 12 total samples, 3 biological replicates each of HSF rho+ and rho0 cells that were not irradiated (control=C) or irradiated (alpha=A). Cells were harvested at 4 hours after treatment.
2011-04-04 | E-GEOD-24945 | biostudies-arrayexpress
Project description:The inflammatory mediator IL6 induced by LPS, which signals via TLR4, has been shown to feedback and augment TLR4 signaling when over-produced in LPS hypersensitive gp130F/F mice. The identity of the LPS/TLR4 responsive inflammatory signaling pathways and gene networks which are modulated by IL6 are unknown. Therefore, to understand the molecular consequences of gp130 hyperactivity in non-haemopoietic tissue on LPS-induced systemic inflammation, global gene expression profiling of livers was performed.
2011-05-17 | GSE29311 | GEO
Project description:Elevated circulating levels of calprotectin (CAL), the S100A8/A9 heterodimer, are biomarkers of severe systemic inflammation. Here, we investigate the effects of CAL on early human hematopoiesis. CAL demonstrates limited impact on gene expression in stem and progenitor cells, in contrast with interleukin-6 (IL6) that promotes the expression of the S100A8 and S100A9 genes in hematopoietic progenitors and the generation of monocytes that release CAL. The main target of CAL is an erythroid-megakaryocyte progenitor (EMP) subset. CAL prevents both erythropoietin-driven differentiation of healthy progenitors and JAK2-V617F-driven erythropoiesis. In the context of JAK2-V617F, CAL also promotes the expression of S100A8 and S100A9 genes in monocytes. The signature of CAL effects is detected in the bone marrow progenitors of patients with myeloid malignancy or severe infection. These results position CAL as a mediator of IL6 effects on triggering anemia during inflammation, an effect that is amplified in the context of JAK2-V617F-driven hematopoiesis.
2024-11-20 | PXD057999 | Pride
Project description:Angiogenesis plays a key role in tumor metastasis. Many genes may act in this process including formation of vessels, immune evasion,etc. Different gene expression profiles between lymphoma endothelium cells and reactive lymph node-derived endothelium cells may uncover these genes. And intensive mechanism researches on such key genes may explain the mechanisim of tumor-specific angiogenesis and help to explore effective treatment strategies to prevent/reverse tumor metastasis. We use microarrays to detail gene expression profiles of human lymphoma endothelium and reactive lymph node-derived endothelium. Lymph nodes were taken from surgery samples of cases pathologically diagnosed DLBCL (diffuse large B-cell lymphoma), PTL (peripheral T cell lymphoma) and reactive lymph nodes. The pure endothelium cells were isolated by LCM after immunohistochemical staining of CD34. We found Tim-3 was preferentially expressed on lymphoma-derived ECs via different expression profiles between lymphoma ECs and reactive lymph node-derived ECs. Intensive researches were carried out on Tim-3-expressing -ECs and we found that Tim-3 -expressing-Ecs may play important role on EC-mediated tumor evasion.
2010-01-14 | E-GEOD-19882 | biostudies-arrayexpress
Project description:Activated eosinophils is a major cell type to be involved in allergic diseases. Type 2 cytokines (IL-4 and IL-5) are important to establish and augment their inflammatory process. The aim of this study is to clarify the role of these cytokines as direct activators for human eosinophils.
2024-06-20 | PXD052200 | JPOST Repository
Project description:Mitochondrial DNA depleted (ρ(0)) human skin fibroblasts (HSF) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-κB and STAT3 signaling pathways, and by decreased activity of mitochondrial death pathway, compared to the parental ρ(+) HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor mediated death pathway remained highly active, and exogenous TRAIL in a combination with cycloheximide (CHX) induced higher levels of apoptosis in ρ(0) cells compared to ρ(+) HSF. Global gene expression analysis using microarray and qRT-PCR demonstrated that mRNA expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, and IGFL2), cytokines (IL6, ΙL17Β, ΙL18, ΙL19, and ΙL28Β) and cytokine receptors (IL1R1, IL21R, and IL31RA) were substantially decreased after mitochondrial DNA depletion. Some of these genes were targets of NF-κB and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation further induced expression of several NF-κB/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in ρ(+) HSF, but this response was substantially decreased in ρ(0) HSF. Suppression of the IKK-NF-κB pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated ρ(+) HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in HSF, especially after alpha-irradiation. Collectively, our results indicated that NF-κB activation was partially lost in ρ(0) HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-κB targets, further suppressing IL6-JAK2-STAT3 that in concert with NF-κB regulated protection against TRAIL-induced apoptosis.
2011-04-04 | GSE24945 | GEO
Project description:During inflammation immune cells can induce endothelial activation and angiogenesis by cytokines and other mediators1,2. The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue infiltrating leukocytes3-5. However, there is limited evidence on initial mechanisms of both processes. Here we show that angiogenesis precedes leukocyte infiltration during graft-versus-host disease (GVHD) and experimental colitis. A key feature of GVHD is the incompletely understood organ tropism to skin, liver and the intestines. We found that angiogenesis initiates GVHD in target organs whereas in non-target organs no angiogenesis and no subsequent inflammation occur, suggesting a previously unrecognized role of the endothelium in GVHD organ tropism. The initiation phase of angiogenesis was not associated to classical endothelial cell (EC) activation signs, such as Vegfa/VEGFR1+2 upregulation or increased adhesion molecule expression. In gene array- and proteomic analyses, we found significant metabolic and cytoskeleton changes in ECs leading to profoundly higher deformation in real-time deformability cytometry6. Our results demonstrate that metabolic changes trigger enhanced migratory and proliferating potential of ECs during the initiation of angiogenesis in GVHD target organs. Our study adds evidence to the hypothesis that angiogenesis can initiate inflammation and provides novel insight in pathophysiology and tropism of GVHD.
2017-01-31 | PXD004606 | Pride
Project description:Although the generation of ETV2-induced endothelial cells (iECs) from human fibroblasts serves as a novel therapeutic strategy in regenerative medicine, the process is inefficient, resulting in incomplete iEC angiogenesis. Therefore, we employed ChIP-sequencing and identified molecular mechanisms underlying ETV2-mediated endothelial transdifferentiation to efficiently produce iECs retaining appropriate functionality in long-term culture. We revealed that the majority of ETV2 targets in human fibroblasts are related to vasculature development and signaling transduction pathways including Rap1 signaling. From a screening of signaling pathway modulators, we confirmed that forskolin facilitated efficient and rapid iEC reprogramming via activation of cAMP/EPAC/RAP1 axis. The iECs obtained via cAMP signaling activation showed superior angiogenesis in vivo as well as in vitro. Moreover, these cells could form aligned endothelium along the vascular lumen ex vivo when seeded into decellularized liver scaffold. Overall, our study provided evidence that cAMP/EPAC/RAP1 axis is required for the efficient generation of iECs with angiogenesis potential.
2019-11-09 | GSE123906 | GEO