Hulme, C, Stevens, A, Dunn, W, Heazell, A, Hollywood, K, Begley, P, Westwood, M and Myers, J (2018) Identification of the functional pathways altered by placental cell exposure to high glucose: lessons from the transcript and metabolite interactome. Scientific Reports, 8 (1). ISSN 2045-2322

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Abstract

The specific consequences of hyperglycaemia on placental metabolism and function are incompletely understood but likely contribute to poor pregnancy outcomes associated with diabetes mellitus (DM). This study aimed to identify the functional biochemical pathways perturbed by placental exposure to high glucose levels through integrative analysis of the trophoblast transcriptome and metabolome. The human trophoblast cell line, BeWo, was cultured in 5 or 25 mM glucose, as a model of the placenta in DM. Transcriptomic analysis using microarrays, demonstrated 5632 differentially expressed gene transcripts (≥± 1.3 fold change (FC)) following exposure to high glucose. These genes were used to generate interactome models of transcript response using BioGRID (non-inferred network: 2500 nodes (genes) and 10541 protein-protein interactions). Ultra performance-liquid chromatography-mass spectrometry (MS) and gas chromatography-MS analysis of intracellular extracts and culture medium were used to assess the response of metabolite profiles to high glucose concentration. The interactions of altered genes and metabolites were assessed using the MetScape interactome database, resulting in an integrated model of systemic transcriptome (2969 genes) and metabolome (41 metabolites) response within placental cells exposed to high glucose. The functional pathways which demonstrated significant change in response to high glucose included fatty acid β-oxidation, phospholipid metabolism and phosphatidylinositol phosphate signalling

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Nature Publishing Group at https://doi.org/10.1038/s41598-018-22535-y Please refer to any applicable terms of use of the publisher.
Subjects: Q Science > Q Science (General)
Depositing User: Symplectic
Date Deposited: 09 Mar 2018 13:03
Last Modified: 20 Jun 2018 14:55
URI: http://eprints.keele.ac.uk/id/eprint/4545

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