Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Serine Metabolism Orchestrates Macrophage Polarization by Regulating the IGF1–p38 Axis

ABSTRACT: Here we show that suppressing the serine biosynthesis pathway, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase or by exogenous serine and glycine restriction, robustly enhances polarization of interferon-g-activated macrophages (M(IFN-g)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo.To further explore its mechanism, we used high-throughput sequencing technology (RNA-seq) to assess gene expression in serine-deficiency or not BMDMs

ORGANISM(S): Mus musculus

PROVIDER: GSE196840 | GEO | 2022/02/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Serine Metabolism Antagonizes Antiviral Innate Immunity Through Preventing ATP6V0d2-mediated YAP Lysosomal Degradation

Project description:Here, we demonstrate that virus-infected macrophages display decreased expression of serine synthesis pathway (SSP) enzymes. Suppressing the SSP key enzyme phosphoglycerate dehydrogenase (PHGDH) by genetic approaches enhanced IFN-b-mediated antiviral innate immunity in vitro and in vivo. To further explore its mechanism, we used high-throughput sequencing technology (RNA-seq) to assess gene expression in PHGDH-deficiency BMDMs and RAW264.7 macrophages.

2021-01-29 | GSE165684 | GEO

Serine Metabolism Orchestrates Macrophage Polarization by Regulating the IGF1–p38 Axis

Project description:Serine Metabolism Orchestrates Macrophage Polarization by Regulating the IGF1–p38 Axis

| PRJNA807522 | ENA

Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism and Growth

Project description:Serine is a non-essential amino acid that is generated by the sequential actions of phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1) and phosphoserine phosphatase (PSPH). Increased serine biosynthesis occurs in several cancers and supports tumor growth. In addition to serine synthesis, exogenous serine is taken up by cells and can also fuel tumor growth. Interestingly, colon cancer cells increase expression of serine biosynthesis enzymes in the absence of exogenous serine, suggesting a compensatory adaptive response to reduced availability of serine. This study explored the relative contributions of exogenous and synthesized serine to colon cancer cell growth, metabolism and response to anti-cancer therapy.

2021-11-04 | GSE144506 | GEO

Transcription of Tnfaip3 is regulated by NF-kB and p38 via C/EBPβ in activated macrophages

Project description:Macrophages play a pivotal role in the immune system through recognition and elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages interact with microbial substances and initiate signal transduction through intracellular adapters. TLR4, which is important for the response to lipopolysaccharide (LPS), triggers downstream signaling mediators and eventually activates IkB kinase (IKK) complex and mitogen-activated protein kinases (MAPKs) such as p38. Previous reports revealed that, in addition to NF-kB, the induction of some LPS-inducible genes in macrophages required another transcription factor whose activity depends on p38. However, these transcription factors remained to be identified. Among these genes, NF-kB and C/EBPβ, a p38 downstream transcription factor, were predicted to co-regulate genes in LPS-stimulated BMDMs. Based on the subsequent results of a chromatin immunoprecipitation assay, we demonstrated that Tnfaip3 is regulated by both NF-kB and p38-dependent C/EBPβ. These results elucidate our understanding of the tight regulation of innate immunity. In order to identify p38-activated transcription factors that cooperate with NF-kB in response to LPS stimulation, microarrays were used to identify genes regulated by both NF-kB and p38 using wild-type, IKK-depleted, and p38 inhibitor-treated mouse bone marrow-derived macrophages (BMDMs). In silico analysis of transcription factor binding sites was used to predict the potential synergistic transcription factors from the co-expressed genes.

2015-04-28 | E-GEOD-46361 | biostudies-arrayexpress

Effect of depletion of OGT on gene expression during M2 polarization of macrophages

Project description:To investigate the function OGT in the regulation of M2 polarization of macrophages, we established IL-4-activated bone marrow-derived macrophages (BMDMs) from mice of wild-type control or Lyz2-Cre/Loxp-mediated knockout of OGT. We then performed gene expression profiling analysis using data obtained from RNA-seq of wild-type (WT) and OGT-knockout (OGT-KO) macrophages at two time points during IL-4 (20ng/μl) sitmulation.

2022-09-08 | GSE210176 | GEO

Serine metabolism supports macrophage IL-1β production.

Project description:Serine is a substrate for nucleotides, NADPH and glutathione (GSH) synthesis. Previous studies in cancer cells and lymphocytes have shown that serine-dependent one-carbon units are necessary for nucleotide production to support proliferation. Presently, it is unknown whether serine metabolism impacts the function of non-proliferative cells, such as inflammatory macrophages. We find that in macrophages, serine is required for optimal lipopolysaccharide (LPS) induction of IL-1β mRNA expression, but not inflammasome activation. The mechanism involves a requirement for glycine, which is made from serine, to support macrophage glutathione (GSH) synthesis. Cell-permeable GSH, but not the one-carbon donor formate, rescues IL-1β mRNA expression. Pharmacological inhibition of de novo serine synthesis in vivo decreased LPS induction of IL-1β levels and improved survival in an LPS-driven model of sepsis in mice. Our study reveals that serine metabolism is necessary for GSH synthesis to support IL-1β cytokine production.

2019-01-15 | GSE125036 | GEO

TIPE1 regulation on macrophage polarization

Project description:Macrophages perform key and distinct functions in maintaining tissue homeostasis through finely tuning their polarization state.Here, we found that tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) was highly expressed in macrophages and Tipe1 depletion impeded M2 polarization of macrophages. The goals of this study are to compare BMDMs from LyzM-Cre; Tipe1f/f or Tipe1f/f mice to have a further view of the potential difference.

2021-09-05 | GSE183208 | GEO

Secretome of P2X7 receptor - Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process

Project description:In order to determine P2X7R secretome we analyzed the proteins present in cell-free supernatants from wild-type (P2rx7+/+) or P2rx7-/- bone marrow-derived macrophages (BMDMs) polarized either to M1 or M2 and subsequently treated with ATP. BMDMs were primed with LPS (M1) or IL-4 (M2) for 4 hours and the proteins secreted during this step were extensively washed with PBS before ATP was added in fresh buffer. The complex mixture of proteins obtained in the macrophages supernatants after ATP stimulation were fractionated using one dimension gel electrophoresis and 10 bands were selected for LC-MS/MS analysis based in their presence in higher intensity in P2rx7+/+ supernatant compared with P2rx7-/- supernatant.

2016-03-11 | PXD001981 | Pride

Differentiation of lncRNAs expression during the polarization macrophages

Project description:To determine lncRNAs transcribed during the polarization of macrophages, we have employed whole genome microarray expression profiling as a discovery platform to identify lncRNAs expression in mouse primary bone marrow derived macrophages (BMDMs) treated with M1 (lipopolysaccharide, LPS) and M2 (IL-4) stimulators.

2019-12-29 | GSE122150 | GEO

PHGDH Arginine Methylation by PRMT1 Promotes Serine Synthesis and Represents a Therapeutic Vulnerability in Hepatocellular Carcinoma

Project description:Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics and transcriptomics analyses, we show a heterogeneity between metabolite and transcript profiles. Specifically, the level of serine in HCC tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is dramatically downregulated. Interestingly, the increased serine level is obtained by enhanced PHGDH catalytic activity due to protein arginine methyltransferase 1 (PRMT1)-mediated methylation of PHGDH at arginine 236. PRMT1-mediated PHGDH methylation and activation potentiates serine synthesis, ameliorates oxidative stress, and promotes HCC growth in vitro and in vivo. FBXO7, an E3 ubiquitin ligase which is downregulated in human HCC tissues, ubiquitinates and downregulates PRMT1 to suppress PHGDH methylation and serine synthesis, leading to the inhibition of HCC cell growth. Furthermore, PRMT1-mediated PHGDH methylation correlates with PHGDH hyperactivation and serine accumulation in human HCC tissues, and is predictive of poor prognosis of HCC patients. Notably, blocking PHGDH methylation with a TAT-tagged non-methylated peptide inhibits serine synthesis and restrains HCC growth, both in an HCC patient-derived xenograft (PDX) model and subcutaneous HCC cell-derived xenograft model. Overall, our findings reveal a novel regulatory mechanism of PHGDH activity and serine synthesis, and suggest PHGDH methylation as a potential therapeutic vulnerability in HCC.

2022-07-11 | GSE207435 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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