Activities per year
Methods: We combined bioinformatics proteomic analysis with in vitro studies and Affymetrix exon-level microarray analyses to investigate the role of protein ox-PTM in angiogenic signalling and development of PE phenotype.
Results: Adenoviral Glrx overexpression disrupted EC angiogenic sprouting, inhibited trophoblast migration and fusion. Glrx mediated angiogenic imbalance by rising sFlt-1:PlGF ratio in EC, while opposite effects were detected in extra-villous trophoblasts. The sFlt-1 changes detected in EC were isoform-specific as the sFlt1-e15a splice variant was elevated while sFlt1-i13 levels remained unchanged. A genome-wide exon-level profiling of overexpressing Glrx transgenic vs littermate control mice placenta revealed a global alteration of alternative splicing events. Bioinformatic analysis identified redox-sensitive targets directly relevant to splicing and PE, and ox-PTM removal was found to disrupt the spliceosome machinery consequently affecting Flt-1 splicing to promote sFlt1-e15a expression.
Conclusions: Glrx-mediated removal of ox-PTMs disrupts placental angiogenic balance in a cell type-specific manner via the modulation of redox-sensitive targets in the spliceosome machinery, which may promote sFlt-e15a release from the placenta and the PE phenotype
|Number of pages||2|
|Journal||Free Radical Biology and Medicine|
|Issue number||Supplement 1|
|Publication status||Published - Dec 2021|
|Event||Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia - Serbia, Belgrade|
Duration: 15 Jun 2021 → 18 Jun 2021
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- 1 Funding - grants and income which support research related activities
Innovation in modelling Placenta for Maternal and Fetal Health (iPLACENTA) (joint with Mimetas BV, St George's Medical School, University College Cork, Universita Degli Studi di Torino, Institut National de le Sante et de la Recherche Medicale, Universitaet Rostock, Fundacion Para le Investigacion del Hospital Universitario La Fe De La Comunidad Valencia, Aston University, Katholieke Universiteit Leuven, Universiteit Maastricht)
Colin Murdoch (Recipient)1 Mar 2018 → 31 May 2022
Activity: Other activity types › Funding - grants and income which support research related activities