دورية أكاديمية
Identification of the functional pathways altered by placental cell exposure to high glucose: lessons from the transcript and metabolite interactome.
| العنوان: | Identification of the functional pathways altered by placental cell exposure to high glucose: lessons from the transcript and metabolite interactome. |
|---|---|
| المؤلفون: | Hulme CH; Maternal and Fetal Health Research Centre, Division of Developmental Biology & Medicine, School of Medical Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.; Maternal and Fetal Health Research Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester Academic Health sciences Centre, Manchester, M13 9WL, UK., Stevens A; Division of Developmental Biology & Medicine, Faculty of Biology, Medicine & Health University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK., Dunn W; Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.; Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M13 9WL, UK.; School of Biosciences, Phenome Centre Birmingham and Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, UK., Heazell AEP; Maternal and Fetal Health Research Centre, Division of Developmental Biology & Medicine, School of Medical Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.; Maternal and Fetal Health Research Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester Academic Health sciences Centre, Manchester, M13 9WL, UK., Hollywood K; Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.; Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M13 9WL, UK.; Manchester Institute of Biotechnology and School of Chemistry, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK., Begley P; Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.; Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M13 9WL, UK., Westwood M; Maternal and Fetal Health Research Centre, Division of Developmental Biology & Medicine, School of Medical Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.; Maternal and Fetal Health Research Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester Academic Health sciences Centre, Manchester, M13 9WL, UK., Myers JE; Maternal and Fetal Health Research Centre, Division of Developmental Biology & Medicine, School of Medical Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK. jenny.myers@manchester.ac.uk.; Maternal and Fetal Health Research Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Manchester Academic Health sciences Centre, Manchester, M13 9WL, UK. jenny.myers@manchester.ac.uk. |
| المصدر: | Scientific reports [Sci Rep] 2018 Mar 27; Vol. 8 (1), pp. 5270. Date of Electronic Publication: 2018 Mar 27. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Metabolome* , Transcriptome*, Glucose/*metabolism , Hyperglycemia/*metabolism , Placenta/*metabolism, Animals ; Cell Line ; Diabetes Complications/genetics ; Diabetes Complications/metabolism ; Diabetes Mellitus/genetics ; Diabetes Mellitus/metabolism ; Female ; Gene Expression Profiling ; Gene Regulatory Networks ; Humans ; Hyperglycemia/genetics ; Lipid Metabolism ; Mice ; Pregnancy ; Pregnancy Complications/genetics ; Pregnancy Complications/metabolism ; Trophoblasts/metabolism |
| مستخلص: | 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. |
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| معلومات مُعتمدة: | MR/M009157/1 United Kingdom MRC_ Medical Research Council |
| المشرفين على المادة: | IY9XDZ35W2 (Glucose) |
| تواريخ الأحداث: | Date Created: 20180329 Date Completed: 20191007 Latest Revision: 20240314 |
| رمز التحديث: | 20240314 |
| مُعرف محوري في PubMed: | PMC5869594 |
| DOI: | 10.1038/s41598-018-22535-y |
| PMID: | 29588451 |
| قاعدة البيانات: | MEDLINE |
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