Early growth response protein-1 coordinates lipotoxicity-associated placental inflammation: Role in Maternal Obesity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE43685 | GEO | 2014/01/21
SECONDARY ACCESSION(S): PRJNA187054
REPOSITORIES: GEO
Similar Datasets
Project description:Maternal obesity during pregnancy leads to a pro-inflammatory milieu in the placenta. We conducted a global transcriptomic profiling in BeWo cells following palmitic acid (PA, 500 uM) and/or TNF-alpha (10 ng/ml) treatment for 24 h. Microarray analysis revealed that placental cytotrophoblasts increased expression of genes related to inflammation, stress response and immediate-early factors in response to plamitic acid, TNF-alpha or a combination of both. Our results suggest that fatty acids and inflammatory cytokines induce inflammation in placental cells via activation of JNK-Egr-1 signaling. global transcriptomic profiling in BeWo cells following palmitic acid (PA, 500 uM) and/or TNF-alpha (10 ng/ml) treatment for 24 h
2014-01-21 | E-GEOD-43685 | biostudies-arrayexpress
Project description:Cellular functions of trophoblasts are regulated by various cytokines and growth factors. We previously reported the synergistic effects of tumor necrosis factor-α (TNF-α) and insulin-like growth factor-I (IGF-I) on BeWo cells proliferation. We performed gene expression array to elucidate the genes involved in the cross-talk of TNF-α and IGF-I in BeWo cells. We identified 553 differentially expressed genes (DEGs) under the co-stimulation of TNF-α and IGF-I. Gene ontology analysis identified “NF-kappa B signaling pathway”, “Calcium signaling pathway”, and “Arachidonic acid metabolism”. Among DEGs, PTGS2 was up-regulated and PTGER2 was down-regulated.
2019-12-10 | GSE119651 | GEO
Project description:Cellular functions of trophoblasts are regulated by various cytokines and growth factors. We previously reported the synergistic effects of tumor necrosis factor-α (TNF-α) and insulin-like growth factor-I (IGF-I) on BeWo cells proliferation. We performed DNA methylation array to elucidate the epigenetic regulation involved in the cross-talk of TNF-α and IGF-I in BeWo cells. We identified general increase in DNA methylation by co-stimulation of TNF-α and IGF-I. Total of 83474 differentially methylated CpG sites were identified in BeWo cells stimulated by IGF-I and high TNF-α. By correlating with the results of expression array, NFKBIE, C3 and GP1BA were identified as differentially methylated genes with significant expression change.
2019-12-10 | GSE119652 | GEO
Project description:The failure of spontaneous resolution underlies chronic inflammatory conditions including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules which promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators which promote the resolution of inflammation. Here we investigated the potential of LXA4 and a synthetic LX analogue [Benzo-LXA4] as therapeutics in a murine model of diabetic kidney disease. Diabetes was induced with streptozotocin in ApoE-/- mice and kidney disease was observed. The development of diabetes-induced albuminuria, mesangial expansion and collagen deposition was attenuated by LXs. It is noteworthy that LXs also attenuated established kidney disease in diabetic mice administered LXs 10 weeks after disease onset, with evidence of preserved kidney function. Kidney transcriptome profiling defined a diabetic signature [725 genes; FDR P≤0.05]. Comparison of this murine gene signature with human DKD identified shared renal pro-inflammatory/pro-fibrotic signals (TNF-α, IL-1β, NF-κB). In diabetic mice we identified 20 and 51 transcripts regulated by LXA4 and Benzo-LXA4, respectively, and pathway analysis identified established (TGF-β1, PDGF, TNF-α, NF-κB) and novel (Early growth response-1 - EGR-1) networks activated in diabetes and regulated by LXs. Using human renal epithelial cells, we demonstrate that LXs attenuate TNF-α driven Egr-1 activation, with Egr-1 important for cellular responses to TGF-β1 and TNF-α. These data demonstrate for the first time that LXs can reverse established diabetic complications and support a therapeutic paradigm to promote the resolution of inflammation.
2018-05-22 | GSE107942 | GEO
Project description:Background: Factors secreted from the placenta into maternal and fetal circulation are important for maternal and fetal development during pregnancy. Maternal hematopoietic stem cells maintain maternal blood supply. The placenta is an early site of fetal hematopoiesis, and placental hematopoietic stem cells are involved in the early stages of fetal blood cell differentiation. Cross-talk between placental cells and hematopoietic stem cells represents an important but understudied phenomenon of pregnancy. The impact of toxicant exposure on placental-immune cell communication is poorly understood. The goals of this study were to 1) determine if factors secreted from placental cells alter transcriptomic responses in hematopoietic stem cells in vitro and 2) if monoethylhexyl phthalate (MEHP), the major metabolite of the pollutant diethylhexyl phthalate, modifies these effects. Methods: Using in vitro cell line models of hematopoietic stem cells (K-562) and placental syncytiotrophoblasts (differentiated BeWo), we treated K-562 cells for 24 hours with media conditioned by incubation with BeWo cells, media conditioned with BeWo cells treated with 10 µM MEHP, or unconditioned controls (n = 4 replicates for each group). We extracted K-562 cell RNA and performed RNA sequencing. We then conducted differential gene expression and pathway analysis by treatment group and accounted for multiple comparisons using false discovery rate (FDR). Results: K-562 cells treated with BeWo cell conditioned media differentially expressed 173 genes (FDR<0.05 and fold-change>2.0), relative to vehicle control. Cells treated with BeWo media upregulated TPM4 2.4 fold (FDR=1.8x10-53) and S1PR3 3.3 fold (FDR=1.6x10-40) compared to controls. Upregulated genes were enriched for biological processes including stem cell maintenance (“somatic stem cell population maintenance”), cell proliferation (“positive regulation of endothelial cell proliferation”) and immune processes (“myeloid leukocyte cytokine production”). Downregulated genes were enriched for protein translation (“mitochondrial translation”) and transcriptional regulation (“RNA processing”). Cells treated with media from BeWo cells treated with MEHP upregulated (FDR<0.05) eight genes, including genes involved in fat/lipid metabolism (PLIN2, fold-change: 1.4; CPT1A, fold-change: 1.4) and iron uptake (TFRC, fold-change: 1.3), relative to the BeWo conditioned media treatment. Conclusion: Hematopoietic stem cells are responsive to media that has been conditioned by placental cells, potentially impacting processes related to stem cell maintenance and proliferation, which may represent placental-immune communication important for development. The metabolite MEHP only had a modest impact on these responses at the single concentration tested. Future directions will investigate components of placental cell media (hormones, microvesicles, and proteins) contributing to hematopoietic cell signals.
2023-05-02 | GSE188187 | GEO
Project description:Maternal obesity and gestational diabetes mellitus (GDM) are associated with adverse intrauterine environments that are high in circulating nutrients. These adverse environments facilitate impairments in placental mitochondrial function and nutrient processing that ultimately leads to an increased risk of the exposed offspring developing non-communicable cardiometabolic health disorders (e.g. obesity, type 2 diabetes, metabolic syndrome). Analysis of fasting serum lipid levels in the third trimester has highlighted that Palmitate (PA) and oleate (OA) are the most abundance non-esterified fatty acids (NEFAs) in circulation. More importantly, these important NEFAs are elevated in both obese and GDM pregnancies. As PA and OA are the most abundant NEFAs in the typical “Westernized Diet” they elevated levels in obese and GDM pregnancies may highlight increased maternal consumption of these fats and could be a link between poor diet and abberant placental function. However, the independent and combined impacts of dietary PA and OA on mitochondrial function and nutrient processing in placental trophoblast cells remains poorly defined. Thus, in this study we sought to utilize a multi-omics approach (combining transcriptomics with untargeted metabolomics and lipidomics) to elucidate the underlying impacts of elevated NEFA levels on BeWo placental trophoblast cells. We highlighted a significant enrichment in the Wikipathways Fatty Acid Biosynthesis Pathway in BeWo cytotrophoblast cells treated with a combination of PA and OA (P/O; 50 µM each). Further, we identified differential expression of genes involved in lipid processing (e.g. ACADVL, ACACB, ACSL5, CREB3L3, PLIN2, and SCD) in BeWo cytotrophoblast cells treated with dietary NEFA species. Overall, these data highlighted that alterations in lipid processing, storage, and oxidation are implicated in the development of placental dysfunction in response to elevated lipid levels.
2023-08-30 | GSE197385 | GEO
Project description:Trophoblast fusion is a central step in placental physiology. This mechanisms can be studied in the BeWO cell model that fuse following forskolin treatment that activates the c-AMP cascade.
2020-12-16 | E-MTAB-9832 | biostudies-arrayexpress
Project description:In this study, we established a rat small intestinal cell (IEC-6) injury model with tumor necrosis factor-α (TNF-α). Then, we added the exosomes from TNF- α damaged IEC-6 (TNF-α-exo), co-cultured with BMMSCs exosomes (BM-exo) and heme oxygenase-1 modified BMMSCs (HBM-exo) system exosomes into IEC-6 cells injured by TNF- α inflammation. After 48 hours, IEC-6 cells were collected for proteomic detection.
2020-06-29 | PXD017002 | Pride
Project description:Chronic intake of a high-fat diet increases saturated fatty acids in the brain causing the progression of neurodegenerative diseases. Palmitic acid is a free fatty acid abundant in the diet that at high concentrations may penetrate the blood brain barrier and stimulate the production of pro-inflammatory cytokines, leading to inflammation in astrocytes. The use of the synthetic neurosteroid tibolone in protection against fatty acid toxicity is emerging, but its transcriptional effects on palmitic acid induced lipotoxicity remain unclear. Herein, we performed a transcriptome profiling of normal human astrocytes to investigate the molecular mechanisms by which palmitic acid causes cellular damage to astrocytes, and whether tibolone could reverse its detrimental effects. Astrocytes undergo a profound transcriptional change at 2 mM palmitic acid, affecting the expression of 739 genes, 366 upregulated and 373 downregulated. However, tibolone at 10 nM does not entirely reverse palmitic acid effects. Additionally, the protein protein interaction reveals two novel gene clustering modules. The first module involves astrocyte defense responses by upregulation of pathways associated with antiviral innate immunity, and the second is linked to lipid metabolism. Our data suggest that activation of viral response signaling pathways might be so far, the initial molecular mechanism of astrocytes in response to a lipotoxic insult by palmitic acid, triggered particularly upon increased expression levels of *IFIT2*, *IRF1*, and *XAF1*. Therefore, this novel approach using a global gene expression analysis may shed light on the pleiotropic effects of palmitic acid on astrocytes, and provide a basis for future studies addressed to elucidate these responses in neurodegenerative conditions, which is highly valuable for the design of therapeutic strategies.
2021-02-10 | GSE166500 | GEO
Project description:<p>The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at <a href="http://clinicaltrials.gov/ct2/show/NCT00083369">clinicaltrails.gov</a>, number NCT00083369). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. A total of 1048 GOLDN participants were included in the diet intervention. The diet intervention followed the protocol of Patsch et al. (<a href="http://www.ncbi.nlm.nih.gov/pubmed/1420093">1992</a>). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 MJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. For the GOLDN lipidomics study, sterols and fatty acids were measured from stored plasma (-80 degrees Celsius) collected at fasting and 3.5 hours after the diet intervention using TrueMass Panels from Lipomics (West Sacramento, CA). A total of 11 sterols were quantified in nmols/gram of sample including total cholesterol, 7-dehydrocholesterol, desmosterol, lanosterol, lathasterol, cholestanol, coprostanol, beta-sitosterol, campesterol, stigmasterol, and 7alpha-hydroxycholesterol. A total of 35 fatty acids were quantified in nmols/gram of sample inlcuding myristic acid (14:0); pentadecanoic acid (15:0); palmitic acid (16:0); stearic acid (18:0); arachidic acid (20:0); behenic acid (22:0); lignoceric acid (24:0); myristoleic acid (14:1n5); palmitoleic acid (16:1n7); palmitelaidic acid (t16:1n7); oleic acid (18:1n9); elaidic acid (t18:1n9); vaccenic acid (18:1n7); linoleic acid (18:2n6); gamma-linolenic acid (18:3n6); alpha-linolenic acid (18:3n3); stearidonic acid (18:4n3); eicosenoic acid (20:1n9); eicosadienoic acid (20:2n6); mead acid (20:3n9); di-homo-gamma-linolenic acid (20:3n6); arachidonic acid (20:4n6); eicsoatetraenoic acid (20:4n3); eicosapentaenoic acid (20:5n3); erucic acid (22:1n9); docosadienoic acid (22:2n6); adrenic acid (22:4n6); docosapentaenoic acid (22:5n6); docosapentaenoic acid (22:5n3); docosahexaenoic acid (22:6n3); nervonic acid (24:1n9); and plasmalogen derivatives of 16:0, 18:0, 18:1n9, and 18:1n7.</p>
| phs000741 | dbGaP