Serine Metabolism Orchestrates Macrophage Polarization by Regulating the IGF1–p38 Axis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA807522 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18048303.fastq.gz | Fastqsanger.gz | |||
| SRR18048304.fastq.gz | Fastqsanger.gz | |||
| SRR18048305.fastq.gz | Fastqsanger.gz | |||
| SRR18048306.fastq.gz | Fastqsanger.gz | |||
| SRR18048307.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description: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
2022-02-19 | GSE196840 | GEO
Project description:Serine metabolism is reportedly involved in immune cell functions, but whether and how serine metabolism regulates macrophage polarization remain largely unknown. Here, we show that suppressing serine metabolism, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase in the serine biosynthesis pathway or by exogenous serine and glycine restriction, robustly enhances the polarization of interferon-γ-activated macrophages (M(IFN-γ)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo. Mechanistically, serine metabolism deficiency increases the expression of IGF1 by reducing the promoter abundance of S-adenosyl methionine-dependent histone H3 lysine 27 trimethylation. IGF1 then activates the p38-dependent JAK-STAT1 axis to promote M(IFN-γ) polarization and suppress STAT6-mediated M(IL-4) activation. This study reveals a new mechanism by which serine metabolism orchestrates macrophage polarization and suggests the manipulation of serine metabolism as a therapeutic strategy for macrophage-mediated immune diseases.
| S-EPMC9622887 | biostudies-literature
Project description:Myocarditis is an inflammatory injury to the myocardium characterized by disrupted intercellular communication, involving macrophages and cardiomyocytes as key players. However, the interactions between macrophages and cardiomyocytes during myocarditis remain inadequately explored. Emerging evidence indicated that extracellular vesicles (EVs) play a crucial role in intercellular communication. Here, we demonstrated that large EVs derived from lipopolysaccharide (LPS)-preconditioned cardiomyocytes (C-lEVLPS) exhibited anti-inflammatory effects on macrophages and alleviated cardiac inflammation and dysfunction in a mouse model of CVB3-induced myocarditis. Additionally, C-lEVLPS facilitated macrophage polarization toward the M2-like phenotype and inhibits M1 polarization, both in vitro and in vivo. label-free proteomics analysis showed, compared to phosphate-buffered saline (PBS)-preconditioned cardiomyocytes (C-lEVPBS), C-lEVLPS was enriched in the phosphatase 2 scaffold subunit alpha protein (PP2AA), which can recruit other subunits to form the PP2A complex, ultimately leading to the dephosphorylates of p38. This study highlights the effect of C-lEVLPS in myocarditis and uncovers the potential mechanism that modulates macrophage polarization by delivering PP2AA from cardiomyocytes to macrophages and regulating the p38 MAPK pathway. These findings provide a promising therapeutic strategy for myocarditis.
2025-09-29 | PXD057460 | Pride
Project description:Insight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays. Lungs from E18.5 were isolated from both Igf1+/+ wild type and Igf1-/- null mice and pooled to obtain RNA. Heterozygous male and female with a genetic background C57BL/6J were mated to obtain embryos at embrionic (E) stage 18.5 days post coitum (E18.5). 3 biological replicates per genotype.
2014-03-31 | E-GEOD-17157 | biostudies-arrayexpress
Project description:The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3PG), the PGAM substrate, to de novo serine synthesis. Blocking de novo serine synthesis from 3PG reversed the effect of PGAM inhibition on Treg polarization, while exogenous serine directly inhibited Treg polarization. Addi-tionally, altering serine levels in vivo with a serine/glycine-free diet increased peripheral Tregs and at-tenuated autoimmunity in a murine model of multiple sclerosis. Mechanistically, we found that serine limits Treg polarization by contributing to one-carbon metabolism and methylation of Treg-associated genes. Inhibiting one-carbon metabolism increased Treg polarization and suppressive function both in vitro and in vivo in a murine model of autoimmune colitis. Our study identifies a novel physiologic role for PGAM and highlights the metabolic interconnectivity between glycolysis, serine synthesis, one-car-bon metabolism, and epigenetic regulation of Treg differentiation and suppressive function
2025-06-06 | GSE269846 | GEO
Project description:Insight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays.
2014-03-31 | GSE17157 | GEO
Project description:A majority of the gas-exchange surface is generated during alveologenesis, and disruption of this process causes bronchopulmonary dysplasia (BPD) in preterm infants, characterized by alveolar simplification. BPD is a significant risk factor for adult emphysema, marked by alveolar loss. A comprehensive molecular understanding of alveologenesis and effective treatments for BPD and emphysema are still lacking. Here, we show that the cells expressing Hhip, a gene associated with both BPD and emphysema, expand within the alveoli during alveologenesis, followed by hedgehog (Hh) inhibition and myofibroblast transition. Stromal-specific deletion of Hhip leads to aberrant persistence of SMA+ alveolar myofibroblasts, mediated by a hyperactive Hh-IGF1 axis. Conditional knockout animal and 3D stroma-stem cell organoid models demonstrate that loss of Hhip induces alveolar stem/progenitor cell senescence in a non–cell-autonomous manner. Alveolar simplification and BPD phenotypes induced by Hhip deletion can be partially rescued by IGF1 signaling blockade. We also observe the downregulation of Hhip expression and hyperactivation of Hh-IGF1 signaling in hyperoxia-induced BPD animal models. In addition, adult mice deficient in Hhip expression develop emphysema phenotype with abnormal alveolar myofibroblasts. Finally, we develop a therapeutic Fc-fused HHIP recombinant protein that attenuates BPD phenotypes in postnatal mice and emphysema in adult mice. These findings underscore the critical role of HHIP in coordinating alveologenesis and preventing BPD and emphysema by restricting Hh-IGF1 signaling.
2025-03-26 | GSE271417 | GEO
Project description:Serine metabolism provides essential metabolites for cellular growth and proliferation, and also produces neurotransmitters. However, how serine metabolism coordinates with functional development of neurons remains unclear. We report neurotransmitter D-serine inhibit growth of immature cells. Metabolomic analysis of neural progenitors revealed that D-serine decreases glycine synthesis thereby diminishes one-carbon metabolism, in which L-serine is a crucial carbon donor. D-serine inhibits one-carbon metabolism by competing transport of cytosolic L-serine to mitochondria, which restrains proliferation and triggers apoptosis of neural progenitors as well as neural tumor cells, but not mature neurons, in vitro and ex vivo. This RNA-seq data supports the idea that D-serine inhibits polarization and growth/proliferation of immature neurons and further indicate that immature neurons counteracts D-serine-induced cellular stress through enhancing mitochondrial function, including energy synthesis.
2024-12-01 | GSE268106 | GEO
Project description:To generate IGF1 signatures in human melanoma cell lines. Recombinant human IGF1 (rhIGF1) was added to WM35, known to be responsive to rhIGF1, whereas constitutive IGF1 signaling in Mel-624 was abrogated by siRNA directed against the IGF1 receptor (siIGF1R). Experiments were performed in triplicate in normoxia (O2 concentration, 21%) and hypoxia (1% O2), because hypoxia has been suspected to play an adverse role in melanoma. After generating GEP data, we created signatures of genes significantly (p ≤0.0001, q ≤0.05) and consistently upregulated in rhIGF1-treated WM35 cells, or similarly downregulated in siIGF1R-treated Mel-624 cells, as compared to control cells at the same O2 concentration.
2018-01-01 | GSE59343 | GEO