Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of histone acetylation status in renal fibroblasts.

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE103058 | GEO | 2019/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type, SphK1-/- and SphK2-/- fibroblasts Transcriptomes

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.

2019-09-01 | GSE103062 | GEO

Sphingolipid metabolism controls mammalian heart regeneration

Project description:Utilization of lipids as energy substrates after birth causes cardiomyocyte (CM) cell-cycle arrest and loss of regenerative capacity in mammalian hearts. Beyond energy provision, proper management of lipid composition is crucial for cellular and organismal health, but its role in heart regeneration remains unclear. Here, we demonstrate widespread sphingolipid metabolism remodeling in neonatal hearts after injury and find that SphK1 and SphK2, isoenzymes producing the same sphingolipid metabolite sphingosine-1-phosphate (S1P), differently regulate cardiac regeneration. SphK2 is downregulated during heart development and determines CM proliferation via nuclear S1P-dependent modulation of histone acetylation. Reactivation of SphK2 induces adult CM cell-cycle re-entry and cytokinesis, thereby enhancing regeneration. Conversely, SphK1 is upregulated during development and promotes fibrosis through an S1P autocrine mechanism in cardiac fibroblasts. By fine-tuning the activity of each SphK isoform, we develop a therapy that simultaneously promotes myocardial repair and restricts fibrotic scarring to regenerate the infarcted adult hearts.

2024-06-04 | GSE180249 | GEO

Sphingosine kinase 2 in stromal fibroblasts creates a hospitable tumor microenvironment in breast cancer

Project description:Reciprocal interactions between breast cancer cells and the tumor microenvironment are important for cancer progression and metastasis. We report here that the deletion or inhibition of sphingosine kinase 2 (SphK2), which produces sphingosine-1-phosphate (S1P), markedly suppresses syngeneic breast tumor growth and lung metastasis in mice by creating a hostile microenvironment for tumor growth and invasion. SphK2 deficiency decreased S1P and concomitantly increased ceramides, including C16-ceramide, in stromal fibroblasts. Ceramide accumulation suppressed activation of cancer-associated fibroblasts (CAFs) by upregulating stromal p53, which restrained production of tumor-promoting factors to reprogram the tumor microenvironment and restrict breast cancer establishment. Ablation of p53 in SphK2-deficient fibroblasts reversed these effects, enabled CAF activation and promoted tumor growth and invasion. These data uncovered a novel role of SphK2 in regulating non-cell autonomous functions of p53 in stromal fibroblasts and their transition to tumor-promoting CAFs, paving the way for the development of a strategy to target the tumor microenvironment and enhance therapeutic efficacy.

2020-01-01 | GSE136655 | GEO

Immune-mediated Tubule Atrophy Promotes Acute Kidney Injury to Chronic Kidney Disease Transition

Project description:Incomplete repair after acute kidney injury (AKI) is associated with progressive loss of tubular cell function and development of chronic kidney disease (CKD). Here, we compared the kidney single-cell transcriptomes from the mice subjected to either unilateral ischemia-reperfusion kidney injury with contralateral nephrectomy (IRI/CL-NX, in which tubule repair predominates) or unilateral IRI with contralateral kidney intact (U-IRI, in which fibrosis and atrophy predominates) to investigate the mechanism(s) underlying transition to CKD following AKI.

2022-06-30 | GSE197626 | GEO

Expression data from C42B prostate cancer cell line treated with enzalutamide and/or sphingosine kinase inhibitor PF-543 or ABC294640

Project description:Epidemiological and molecular evidence indicate that sphingolipids may play a role in the resistance of prostate cancer to androgen receptor signalling inhibitors such as enzalutamide, through the metabolism of ceramide into sphingosine-1-phosphate (S1P) which activates specific G-protein coupled receptors present on cancer cells and immune cells. Sphingosine kinase inhibitors which prevent the production of S1P have anti-cancer effects in vitro and in animal models. Our work showed that SPHK inhibitors can enhance the efficacy of enzalutamide in prostate cancer cell lines. We used microarrays to investigate the transcriptomic changes from the combination of enzalutamide with the SPHK1 inhibitor PF543, or SPHK2 inhibitor ABC294640, in C42B, one of the prostate cancer cell line.

2021-10-14 | GSE173886 | GEO

The transcriptional response to unilateral nephrectomy with and without ischemia-reperfusion injury

Project description:Transcriptome analysis was done after warm renal ischemia-reperfusion injury (IRI) in a rat model. Earlier studies have shown a protective effect of prior unilateral nephrectomy (UNx) against IRI in the remaining, contralateral kidney compared to a non-neprectomized control group. We aimed at identifying the underlying molecular mechanisms. We used the Affymetrix Clariom D array (formerly known as RTA 1.0 st.) Array data was processed in the Affymetrix Console Software.

2017-11-04 | GSE100540 | GEO

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp2]

Project description:Sexual dimorphism in kidney injury markers, such as Klotho, is frequently underestimated or disregarded, as most of the preclinical research is done in male animals. Klotho is well-linked to renal health and its deletion in mice results in a severe accelerated aging-like phenotype and premature death. Here, we identified candidate Klotho enhancers and discovered their function using mice carrying deletions in the enhancer loci. Candidate Klotho enhancers were deleted using CRISPR/Cas9 genome editing. Warm ischemia-reperfusion surgery (IRI) was performed bilaterally to induce acute kidney injury and unilaterally in a fibrosis model. Using ChIP-seq and RNA-seq, we analyzed renal chromatin features and gene expression. ELISA and colorimetric assays were used to measure serum FGF23 and serum component levels. Removal of the enhancer caused more substantial reduction in Klotho mRNA levels in female mice compared to males (90 vs. 50%), supported by gene promoter marks remaining more pronounced in males. Weight, lifespan, and fertility of mice lacking the enhancers were not impacted. Only male mutant mice displayed higher Havcr1 expression after IRI than controls (mean 1048 vs. 231.4, p=0.0016). 28 days after unilateral IRI, only males displayed increased fibrosis markers, but with no difference between genotypes. Our findings reveal sexual dimorphism of Klotho gene expression and its enhancer regulation. Only male mutant mice were more susceptible to acute injury and the enhancer deletion had no impact on fibrosis. Additional investigation into the mechanisms governing Klotho regulation is imperative to reassess its effectiveness as a kidney injury marker.

2024-04-04 | GSE255885 | GEO

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [RNA exp1]

2024-04-04 | GSE243945 | GEO

Deletion of Klotho enhancer deepens sexual dimorphism of gene expression without impacting female resistance to kidney injury [ChIP]

2024-04-04 | GSE243944 | GEO

Transcriptional signature of hypoxic preconditioning in a mouse model of ischemic acute kidney injury

Project description:We have performed NGS-derived transcriptome profiling (RNA-seq) to examine the impact of hypoxic preconditioning in post-ischemic kidney injury. Experimental set up: 4 C57BL/6J (male, 8 wks of age) mice were subjected to hypoxia (8%O2) for 48hrs and then subjected to unilateral renal ischemic reperfusion mice (IRI). 4 normoxic littermates subjected to renal IRI served as controls. Injured kidneys were harvested at day 3 following renal IRI and were subjected to NGS. Methods: Poly(A) RNA sequencing library was prepared following Illumina’s TruSeq-stranded-mRNA sample preparation protocol. Quality control analysis and quantification of the sequencing library were performed using Agilent Technologies 2100 Bioanalyzer High Sensitivity DNA Chip. Paired-ended sequencing was performed on Illumina’s NovaSeq 6000 sequencing system.

2021-07-19 | GSE156516 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data