Expression data from PPARg WT and KO macrophages
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE24292 | GEO | 2010/09/24
SECONDARY ACCESSION(S): PRJNA130003
REPOSITORIES: GEO
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Project description:PPARg is a nuclear receptor that plays an important role in lipid metabolism, homeostasis and immunity. Microarray analysis of gene expression was performed in macrophages from WT and PPARg KO mice. Differentially expressed genes were selected for further analysis. RNA from WT and PPARg KO macrophages was purified for hybridization on Affymetrix microarrays. Peritoneal macrophages were harvest from WT and PPARg KO mice 3 days after intraperitoneal injection of 2.5ml of 3% thioglycollate.
2010-09-24 | E-GEOD-24292 | biostudies-arrayexpress
Project description:Peroxisome proliferator-activated receptor-gamma (PPARg) regulates the interface between cellular lipid metabolism, redox status and organelle differentiation. Following conditional prostatic epithelial knockout of PPARg in mice we observed focal hyperplasia of the epithelium which developed to mouse prostatic intraepithelial neoplasia (mPIN), becoming progressively more severe with time. We selectively knocked down PPARg2 isoform in wild-type mouse prostatic epithelial cells and examined the consequences of this in a tissue recombination model. Histopathologically the results resembled the conditional PPARg KO mouse prostates. Electron microscopy showed accumulated defective lysosomes and autophagic vacuoles in both of PPARg- and g2- deficient cells. Gene expression profiling indicated a major dysregulation of cell cycle control and metabolic signaling networks related to peroxisomal and lysosomal maturation, lipid oxidation and degradation. We conclude that PPARg maintains the maturation and turnover of peroxisomes and lysosomes in prostate epithelium. Disruption of PPARg signaling results in autophagy and oxidative stress during mPIN pathogenesis. The mPrE-PPARg knockout and mPrE-PPARg2 shRNA cells were compared to wildtype mPrE cells. Time (3 days culture) and cell types (x 4) were tested.
2010-05-18 | E-GEOD-13867 | biostudies-arrayexpress
Project description:Peroxisome proliferator-activated receptor-gamma (PPARg) regulates the interface between cellular lipid metabolism, redox status and organelle differentiation. Following conditional prostatic epithelial knockout of PPARg in mice we observed focal hyperplasia of the epithelium which developed to mouse prostatic intraepithelial neoplasia (mPIN), becoming progressively more severe with time. We selectively knocked down PPARg2 isoform in wild-type mouse prostatic epithelial cells and examined the consequences of this in a tissue recombination model. Histopathologically the results resembled the conditional PPARg KO mouse prostates. Electron microscopy showed accumulated defective lysosomes and autophagic vacuoles in both of PPARg- and g2- deficient cells. Gene expression profiling indicated a major dysregulation of cell cycle control and metabolic signaling networks related to peroxisomal and lysosomal maturation, lipid oxidation and degradation. We conclude that PPARg maintains the maturation and turnover of peroxisomes and lysosomes in prostate epithelium. Disruption of PPARg signaling results in autophagy and oxidative stress during mPIN pathogenesis.
2009-12-07 | GSE13867 | GEO
Project description:Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network, we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages (Lefterova et al. 2010 (PMID 20176806); GSE21314). We found that PPARg binding was highly divergent and only 5% of the PPARg-bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition, conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this PPARg and PU.1 binding between human and mouse, we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages. Genome-wide location analysis for 3 transcription factors (PPARg, RXR and PU.1) in a human monocytic cell line (THP-1). This submission represents the human binding data component of the study.
2011-12-01 | E-GEOD-25426 | biostudies-arrayexpress
Project description:Macrophages exhibit a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements that support this process have remained incompletely understood. Here, we showed that posttranslational modification (PTM) of peroxisome proliferator-activated receptor g (PPARg) regulated lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrated the function of reparative macrophages. In injured tissues, repair signaling attenuated macrophage PPARg threonine 166 (T166) phosphorylation, which induced a partially active PPARg program with increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby activating lipogenesis. The accumulated lipids served as signaling molecules, triggering signal transducer and activator of transcription 3 (STAT3)-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for the secretion of proteins. Genetic or pharmacological inhibition of PPARg T166 phosphorylation promoted the reparative function of macrophages and facilitated tissue regeneration. In summary, we identified that PPARg T166-regulated lipid biosynthesis was essential for the anabolic demands of the activation and function of macrophages and provided a rationale for therapeutic targeting of tissue repair.
2024-07-30 | GSE252900 | GEO
Project description:Macrophages exhibit a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements that support this process have remained incompletely understood. Here, we showed that posttranslational modification (PTM) of peroxisome proliferator-activated receptor g (PPARg) regulated lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrated the function of reparative macrophages. In injured tissues, repair signaling attenuated macrophage PPARg threonine 166 (T166) phosphorylation, which induced a partially active PPARg program with increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby activating lipogenesis. The accumulated lipids served as signaling molecules, triggering signal transducer and activator of transcription 3 (STAT3)-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for the secretion of proteins. Genetic or pharmacological inhibition of PPARg T166 phosphorylation promoted the reparative function of macrophages and facilitated tissue regeneration. In summary, we identified that PPARg T166-regulated lipid biosynthesis was essential for the anabolic demands of the activation and function of macrophages and provided a rationale for therapeutic targeting of tissue repair.
2024-07-30 | GSE252899 | GEO
Project description:Macrophages exhibit a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements that support this process have remained incompletely understood. Here, we showed that posttranslational modification (PTM) of peroxisome proliferator-activated receptor g (PPARg) regulated lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrated the function of reparative macrophages. In injured tissues, repair signaling attenuated macrophage PPARg threonine 166 (T166) phosphorylation, which induced a partially active PPARg program with increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby activating lipogenesis. The accumulated lipids served as signaling molecules, triggering signal transducer and activator of transcription 3 (STAT3)-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for the secretion of proteins. Genetic or pharmacological inhibition of PPARg T166 phosphorylation promoted the reparative function of macrophages and facilitated tissue regeneration. In summary, we identified that PPARg T166-regulated lipid biosynthesis was essential for the anabolic demands of the activation and function of macrophages and provided a rationale for therapeutic targeting of tissue repair.
2024-07-30 | GSE269832 | GEO
Project description:Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages. We found that PPARg binding was highly divergent and only 5% of the PPARg bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this of PPARg and PU.1 binding between human and mouse we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages. Comparison of RNAs level in Rosiglitazone (RSG) and vehicle (DMSO) treated PMA differentiated THP-1 cells over a timecourse from 0.5h to 12h
2011-12-01 | E-GEOD-25137 | biostudies-arrayexpress
Project description:Tissue resident macrophages are a heterogeneous population with unique functions. During steady state conditions most tissue macrophages are of embryonic origin and maintained locally. Despite their common fetal origin, tissue macrophages are able to fulfil tissue specific functions, suggesting that the local environment can modulate cell function. It has been reported that PPARg is critical for the development of macrophages in the lung. Here, we show that PPARg functions as a transcriptional repressor in alveolar macrophages. Alveolar macrophages lacking Pparg responded more strongly to LPS stimulation by producing more cytokines and phagocytosed more particles in vitro. Certain prostaglandins can act as endogenous ligands for PPARg. We show that prostaglandins were expressed in an organ-specific fashion and modulated cytokine production by alveolar macrophages as well as bone marrow-derived macrophages and monocytic U937 cells. Pparg expression was further induced in macrophages by different cytokine combinations including IL-4, IL-3 and IL-13 suggesting a global role for PPARg which can be regulated by the local environment on two levels. Lastly, repression of inflammatory genes was mediated by PPARg interacting with NFkB and STAT signalling cascades rather than direct transrepression. Therefore PPARg is a modulator of macrophage functions, that changes the inflammatory state of macrophages by regulating classical immune signalling cascades.
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Project description:Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by accumulation of surfactant lipoproteins within the lung alveoli. Alveolar macrophages (AMs) are crucial for surfactant clearance and their differentiation depends on colony-stimulating factor 2 (CSF2) and the establishment of an AM-characteristic gene regulatory network. Here we report that the transcription factor C/EBPβ is essential for the development of the AM identity, as demonstrated by transcriptome and chromatin accessibility analysis. Furthermore, C/EBPβ-deficient AMs showed severe defects in proliferation, phagocytosis and lipid metabolism, collectively resulting in a PAP-like syndrome. Mechanistically, the long C/EBPβ protein variants LAP* and LAP together with CSF2 signaling induced expression of Pparg isoform2, but not isoform1, a molecular regulation that was also observed in other CSF2-primed macrophages. These results uncover C/EBPβ as a key regulator of AM cell fate and as the missing link between CSF2 and Pparg isoform 2 expression, thereby regulating lipid turnover in AMs.
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