RNA sequencing of Sphk1fl/fl Sphk2-/- and Sphk1-/- Sphk2-/- mESC clones.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139964 | GEO | 2019/11/06
REPOSITORIES: GEO
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Project description:The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine kinase 1 activity. SphK1 is a sphingolipid enzyme that converts sphingosine to bioactive sphingosine-1-phosphate (S1P). Recent data suggest a potential relationship between SphK1 and TNFα and have implicated SphK1/S1P in the development and progression of inflammation. Here we further study the relationship of TNFα and SphK1 using an in vivo model. Transgenic hTNFα mice, which develop a spontaneous arthritis (limited to paws) at 20 weeks, were crossed with SphK1 activity null mice (SphK1-/-) to study the development of inflammatory arthritis in the functional absence of SphK1. Results show that hTNF/SphK1-/- have significantly less severity and progression of arthritis and bone erosions as measured through micro-CT images. Additionally, less COX-2 protein, mTNFα transcript levels and fewer Th 17 cells were detected in the joints of hTNF/SphK1-/- compared to hTNF/SphK1+/+ mice. Microarray analysis of the ankle joint showed that hTNF/SphK1-/- mice have increased transcript levels of IL-6 and SOCS3 compared to hTNF/SphK1+/+ mice. Finally, fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1-/- mice compared to hTNF/SphK1+/+ mice. These data show that SphK1 plays a role in hTNFα induced inflammatory arthritis, potentially through a novel pathway involving IL-6 and SOCS3. Two wild-type replicates; three replicates of human TNFa transgene overexpression and normal sphingosine kinase 1; three replicates of human TNFa transgene overexpression and sphingosine kinase 1 null.
2011-01-15 | E-GEOD-20152 | biostudies-arrayexpress
Project description:The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine kinase 1 activity. SphK1 is a sphingolipid enzyme that converts sphingosine to bioactive sphingosine-1-phosphate (S1P). Recent data suggest a potential relationship between SphK1 and TNFα and have implicated SphK1/S1P in the development and progression of inflammation. Here we further study the relationship of TNFα and SphK1 using an in vivo model. Transgenic hTNFα mice, which develop a spontaneous arthritis (limited to paws) at 20 weeks, were crossed with SphK1 activity null mice (SphK1-/-) to study the development of inflammatory arthritis in the functional absence of SphK1. Results show that hTNF/SphK1-/- have significantly less severity and progression of arthritis and bone erosions as measured through micro-CT images. Additionally, less COX-2 protein, mTNFα transcript levels and fewer Th 17 cells were detected in the joints of hTNF/SphK1-/- compared to hTNF/SphK1+/+ mice. Microarray analysis of the ankle joint showed that hTNF/SphK1-/- mice have increased transcript levels of IL-6 and SOCS3 compared to hTNF/SphK1+/+ mice. Finally, fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1-/- mice compared to hTNF/SphK1+/+ mice. These data show that SphK1 plays a role in hTNFα induced inflammatory arthritis, potentially through a novel pathway involving IL-6 and SOCS3.
2011-01-15 | GSE20152 | GEO
Project description:RNA sequencing of Sphk1fl/fl Sphk2-/- and Sphk1-/- Sphk2-/- mESC clones.
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Project description:In numerous forms of organ injury, interstitial fibrosis is a final common pathway. Despite recent epidemiological studies, therapies to focus on fibrosis and to delay progressive renal failure are limited. Previously our group showed that sphingosine kinase 2 deficient-mice (SphK2-/-) develop less fibrosis in folic acid-induced or unilateral ischemia-reperfusion injury (IRI)-induced kidney fibrosis models. Sphingosine 1-phosphate (S1P) is produced by two sphingosine kinase isoforms (SphK1 and SphK2). S1P is involved in diverse functions, but the role of S1P produced by SphK2 is gathering attention as treatments focused on epigenetics have been developed. SphK2 is primarily located in the nucleus and S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes in histone acetylation status, which can lead to an altered target gene expression. We identified that bone marrow stromal cell antigen-1 (Bst1/CD157) is a gene related with kidney fibrosis based on the combination of genome-wide analysis and in vivo screening. SphK2 regulates Bst1 expression and Bst1-/- mice develop less fibrosis after unilateral IRI and are protected against renal bilateral IRI. Bone marrow chimera experiments further revealed the importance of Bst1 expression on hematopoietic cells. Furthermore we identified the role of Bst1 expression in neutrophils for inducing renal ischemia-reperfusion injury and fibrosis.
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Project description:Sphingosine Kinase-1 knock out protects against hyperoxic lung injury One day old Wild type (WT) control and Sphingosine Kinase-1 knock out (SphK-1 KO)pups exposed to room air (RA) or hyperoxia (HO). Microarray based profiling of lung tissue after 7 days of hyperoxia of 75%
2016-10-30 | GSE87350 | GEO
Project description:Advanced head and neck squamous cell carcinomas (HNSCC) are frequently drug resistant and have a mortality rate of 40%. We have previously shown that E2F7 may contribute to drug sensitivity. In the present study, we conducted an –omics screen to identify factors that were responsible for E2F7-dependent resistance to anthracyclines by HNSCC. We provide, in vitro, in vivo and patient data that identifies the existence of a novel E2F7/Sphingosine kinase 1/Sphingosine-1-phosphate/AKT axis that regulates sensitivity to anthracyclines in HNSCC. Specifically, we show that E2F7-dependent sensitivity to doxorubicin occurs via induction of the sphingosine kinase 1/AKT axis. We also show that pharmacological inhibition of Sphingosine kinase 1 or AKT sensitizes SCC cells to the cytotoxic actions of doxorubicin in vitro and in vivo. Combined, these findings highlight a novel mechanism through which SCC cells acquire resistance to anthracyclines and identify specific pharmacological combinations that could be used to treat SCC.
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Project description:The oncogenic roles of Sphingosine kinase 1 (SphK1) in various cancers, including thyroid cancer, have been well demonstrated. However, miRNAs associated with the oncogenic roles of SphK1 remains largely unknown. The goal of this study is to detect the global gene and microRNA (miRNA) expression in response to Sphk1 over-expression and identify potential therapeutic targets. To achieve this, SphK1 was stably overexpressed in papillary thyroid cancer cell line TPC1. Then the mRNA and miRNA expression were quantified using digital gene expression (DGE) analysis and small RNA-seq in TPC1-Vector and TPC1-SphK1 cells, respectively. miRNA-mRNA interactions were explored by microT-CDS and the predicted networks were visualized using CytoScape. In this study, we found that over-expression of SphK1 differentially regulates 46 miRNAs and 506 mRNAs expression in TPC1 cells. Combining bioinformatics prediction of mRNA targets and DGE data on mRNA expressions allowed to identify mRNA targets of deregulated miRNAs. The direct interaction between miR-144-3p and FN1 mRNA, which mediates the pro-invasive role of SphK1 in thyroid cancer cells, was experimentally validated. In general, our results provided a miRNA-mRNA regulatory network in response to SphK1 overexpression in thyroid cancer cells. We also demonstrated a role of miR-144-3p and FN1 in mediating oncogenic function of SphK1, which enhance the understanding of etiology of thyroid cancer.
2016-09-24 | GSE87307 | GEO
Project description:The oncogenic roles of Sphingosine kinase 1 (SphK1) in various cancers, including thyroid cancer, have been well demonstrated. However, miRNAs associated with the oncogenic roles of SphK1 remains largely unknown. The goal of this study is to detect the global gene and microRNA (miRNA) expression in response to Sphk1 over-expression and identify potential therapeutic targets. To achieve this, SphK1 was stably overexpressed in papillary thyroid cancer cell line TPC1. Then the mRNA and miRNA expression were quantified using digital gene expression (DGE) analysis and small RNA-seq in TPC1-Vector and TPC1-SphK1 cells, respectively. miRNA-mRNA interactions were explored by microT-CDS and the predicted networks were visualized using CytoScape. In this study, we found that over-expression of SphK1 differentially regulates 46 miRNA and 506 mRNAs expression in TPC1 cells. Combining bioinformatics prediction of mRNA targets and DGE data on mRNA expressions allowed to identify mRNA targets of deregulated miRNAs. The direct interaction between miR-144-3p and FN1 mRNA, which mediates the pro-invasive role of SphK1 in thyroid cancer cells, was experimentally validated. In general, our results provided a miRNA-mRNA regulatory network in response to SphK1 overexpression in thyroid cancer cells. We also demonstrated a role of miR-144-3p and FN1 in mediating oncogenic function of SphK1, which enhance the understanding of etiology of thyroid cancer.
2016-09-24 | GSE87310 | GEO
Project description:Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of a restricted set of genes independently of its known effects on canonical signaling through sphingosine-1-phosphate (S1P) receptors. We found that FTY720 is phosphorylated in Era-negative breast cancer cells by nuclear sphingosine kinase 2 and accumulates these cells.
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