Pregnancy-specific glycoprotein function, conservation and receptor investigation

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dc.contributor.advisor Moore, Thomas F. en O'Riordan, Ronan T. 2015-08-31T13:26:29Z 2015-08-31T13:26:29Z 2014 2014
dc.identifier.citation O'Riordan, R. T. 2014. Pregnancy-specific glycoprotein function, conservation and receptor investigation. PhD Thesis, University College Cork. en
dc.identifier.endpage 176
dc.description.abstract Pregnancy-specific glycoproteins (PSGs) are highly glycosylated secreted proteins encoded by multi-gene families in some placental mammals. They are carcinoembryonic antigen (CEA) family and immunoglobulin (Ig) superfamily members. PSGs are immunomodulatory, and have been demonstrated to possess antiplatelet and pro-angiogenic properties. Low serum levels of these proteins have been correlated with adverse pregnancy outcomes. Objectives: Main research goals of this thesis were: 1). To attempt to replicate previously reported cytokine responses to PSG-treatment of immune cells and subsequently to investigate functionally important amino acids within PSG1. 2). To determine whether candidate receptor, integrin αvβ3, was a binding partner for PSG1 and to investigate whether PSG1 possessed functionality in a leukocyte-endothelial interaction assay. 3). To determine whether proteins generated from recently identified putative PSG genes in the horse shared functional properties with PSGs from other species. Outcomes: 1). Sequential domain deletion of PSG1 as well as mutation of conserved residues within the PSG1 Ndomain did not affect PSG1-induced TGF-β1. The investigated response was subsequently found to be the result of latent TGF-β1 contaminating the recombinant protein. Protein further purified by SEC to remove this showed no induction of TGF-β1. The most N-terminal glycosylation site was demonstrated to have an important role in PSG N domain secretion. PSG1 attenuated LPS-induced IL-6 and TNF-α. Investigations into signalling underpinning this proved inconclusive. 2). Integrin αvβ3 was identified as a novel PSG1 receptor mediating an as yet unknown function. Preliminary investigations into a role for PSGs as inhibitors of leukocyte endothelial interactions showed no effect by PSG1. 3). Horse PSG protein, CEACAM49, was shown to be similarly contaminated by latent TGF-β1 particle and once removed did not demonstrate TGF-β1 release. Interestingly horse PSG did show anti-platelet properties through inhibition of the plateletfibrinogen interaction as previously published for mouse and human PSGs. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Ronan T. O'Riordan. en
dc.rights.uri en
dc.subject Integrin en
dc.subject Evolution en
dc.subject TGF-beta1 en
dc.subject Glycosylation en
dc.subject IL-6 en
dc.subject TNF-alpha en
dc.subject Secretion en
dc.subject Pregnancy-specific gycoprotein en
dc.title Pregnancy-specific glycoprotein function, conservation and receptor investigation en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral Degree (Structured) en
dc.type.qualificationname PhD Scholars Programme in Cancer Biology en
dc.internal.availability Full text available en No embargo required en
dc.description.version Accepted Version
dc.contributor.funder Health Research Board en
dc.description.status Not peer reviewed en Biochemistry en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
dc.internal.conferring Summer Conferring 2014

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© 2014, Ronan T. O'Riordan. Except where otherwise noted, this item's license is described as © 2014, Ronan T. O'Riordan.
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