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Early growth response protein-1 coordinates lipotoxicity-associated placental inflammation: Role in Maternal Obesity

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Kartik Shankar

PROVIDER: E-GEOD-43685 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Early growth response protein-1 coordinates lipotoxicity-associated placental inflammation: Role in Maternal Obesity

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.

2014-01-21 | GSE43685 | GEO

Gene expression analysis of BeWo cells stimulated by tumor necrosis factor-alpha and insulin-like growth factor-I

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.

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Elevated Dietary Non-Esterified Fatty Acid Levels Impact BeWo Trophoblast Metabolism and Lipid Processing: A Multi-OMICS Outlook

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.

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H3K9me3 in vitro ChIP-Sequencing data [SCC-25]

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H3K4me3 in vitro ChIP-Sequencing data [EGR2 KD]

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EGR2 in vitro ChIP-Sequencing data [SCC-25 (pLKO.1)]

Project description:EGR2 profiling of OSCC cells following in vitro exposure to palmitic acid (PA) for 4 days and after 14 days of palmitic acid withdrawal.

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