Expression data of lung tissues of rats exposed to chronic hypoxia
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ABSTRACT:
ORGANISM(S): synthetic construct Rattus norvegicus
PROVIDER: GSE128451 | GEO | 2019/03/19
REPOSITORIES: GEO
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Project description:In this study, miRNA-seq technique was used to identify differentially expressed miRNAs (DE miRNAs) in cardiac muscle of the Tibetan pig (TP) and Yorkshire pig (YP), which were both raised in highland environments. We obtained 108 M clean reads and 372 unique miRNAs that included 210 known pre-miRNAs and 162 novel pre-miRNAs. In addition, 20 DE miRNAs, including 10 upregulated and 10 downregulated miRNAs, were identified by comparing TP and YP. Based on the expression abundance and differentiation between the two populations, we predicted their targets, and KEGG pathway analyses suggested that DE miRNAs between the Tibetan pigs and Yorkshire pigs are involved in hypoxia-related pathways, such as the MAPK, mTOR, and VEGF signaling pathways, cancer-related signaling pathways, etc. Five DE miRNAs were randomly selected to validate the veracity of miRNA-seq using real-time PCR. The results showed that the expression corresponds to the trend in miRNA-seq, hence the deep-sequencing methods were feasible and efficient. This study expanded the number of hypoxic-adaptation-related miRNAs in pig and indicated that the expression patterns of hypoxia-related miRNAs are significantly altered in the Tibetan pig. DE miRNAs may play important roles in hypoxic adaptation after migration to hypoxic environments. mRNA profiles of 6-month old Tibetan pig (TP) and Yorkshire pig (YP) were generated by deep sequencing, in duplicate, using Hiseq 2000.
2015-07-31 | E-GEOD-71550 | biostudies-arrayexpress
Project description:In this study, miRNA-seq technique was used to identify differentially expressed miRNAs (DE miRNAs) in cardiac muscle of the Tibetan pig (TP) and Yorkshire pig (YP), which were both raised in highland environments. We obtained 108 M clean reads and 372 unique miRNAs that included 210 known pre-miRNAs and 162 novel pre-miRNAs. In addition, 20 DE miRNAs, including 10 upregulated and 10 downregulated miRNAs, were identified by comparing TP and YP. Based on the expression abundance and differentiation between the two populations, we predicted their targets, and KEGG pathway analyses suggested that DE miRNAs between the Tibetan pigs and Yorkshire pigs are involved in hypoxia-related pathways, such as the MAPK, mTOR, and VEGF signaling pathways, cancer-related signaling pathways, etc. Five DE miRNAs were randomly selected to validate the veracity of miRNA-seq using real-time PCR. The results showed that the expression corresponds to the trend in miRNA-seq, hence the deep-sequencing methods were feasible and efficient. This study expanded the number of hypoxic-adaptation-related miRNAs in pig and indicated that the expression patterns of hypoxia-related miRNAs are significantly altered in the Tibetan pig. DE miRNAs may play important roles in hypoxic adaptation after migration to hypoxic environments.
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Project description:Hyperactivation of Notch signaling and the cellular hypoxic response are frequently observed in cancers, with increasing reports of connections to tumor initiation and progression. The two signaling mechanisms are known to intersect, but while it is well established that hypoxia regulates Notch signaling, less is known about whether Notch can regulate the cellular hypoxic response. We now report that Notch signaling specifically controls expression of HIF2a, a key mediator of the cellular hypoxic response. Transcriptional upregulation of HIF2a by Notch under normoxic conditions leads to elevated HIF2a protein levels in primary breast cancer cells as well as in human breast cancer, medulloblastoma and renal cell carcinoma cell lines. The elevated level of HIF2a protein was in certain tumor cell types accompanied by down-regulation of HIF1a protein levels, indicating that high Notch signaling may drive a HIF1a-to-HIF2a switch. At the transcriptome level, the presence of HIF2a was required for approximately 21% of all Notch-induced genes: among the 1062 genes that were upregulated by Notch in medulloblastoma cells during normoxia, upregulation was abrogated in 227 genes when HIF2a expression was knocked down by HIF2a siRNA. In conclusion, our data show that Notch signaling affects the hypoxic response via regulation of HIF2a, which may be important for future cancer therapies.
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Project description:We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone.
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Project description:We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone. 6 neuroblastoma tumors were transfected with Notch1 decoy, 6 with Notch1 decoy and treated with bevacizumab, 6 tumors treated with bevacizumab, and 6 control tumors were profiled by human 133A 2.0 arrays
2013-12-01 | E-GEOD-48880 | biostudies-arrayexpress
Project description:Hypoxia (low oxygen) and Notch signaling are two important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increases Notch signaling, in a process requiring the vasoactive hormone adrenomedullin but not endogenous VEGF. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, functional Notch signaling was required for hypoxia to upregulate the arterial marker genes Depp, connexin40 (Gja5), Cxcr4 and Hey1. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxiamediated induction of the arterial differentiation program.
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Project description:In this study, we measured liver miRNA in male B6C3F1 mice exposed to a known chemical activator of the peroxisome proliferator-activated receptor alpha (PPARα) pathway, di(2-ethylhexyl) phthalate (DEHP), for 7 and 28 days at concentrations of 0, 750, 1500, 3000, or 6000 ppm in feed. At the highest dose tested, DEHP altered 61 miRNAs after 7 days and 171 miRNAs after 28 days of exposure, with 48 overlapping miRNAs between timepoints. Analysis of these 48 common miRNAs indicated enrichment in PPARα targets and other pathways related to liver injury and cancer. Four of the 10 miRNAs exhibiting a clear dose trend were linked to PPARα activation: mmu-miRs-125a-5p, -182-5p, -20a-5p, and -378a-3p.
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Project description:Hypoxia (low oxygen) and Notch signaling are two important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increases Notch signaling, in a process requiring the vasoactive hormone adrenomedullin but not endogenous VEGF. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, functional Notch signaling was required for hypoxia to upregulate the arterial marker genes Depp, connexin40 (Gja5), Cxcr4 and Hey1. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxiamediated induction of the arterial differentiation program. 12 microarray samples consisting of >50,000 FACS sorted CD31+ cells purified from wild type mouse CCE ES cells that were differentiated into the endothelial lineages in 3 biological replicates. The ES cells were subjected to embryoid body formation over 4 days in hanging drop cultures, FACS sorted for Flk1 positive vascular progenitors cells and plated for a further 4 days in normoxia (21% oxygen) or hypoxia (1.5-2% oxygen) with or without 4 umol/l gamma-secretase inhibitor L-685.458.
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