Pregnancy-specific glycoprotein function, conservation and receptor investigation

O'Riordan, Ronan T.

Pregnancy-specific glycoprotein function, conservation and receptor investigation

dc.check.embargoformat	Not applicable	en
dc.check.info	No embargo required	en
dc.check.opt-out	Not applicable	en
dc.check.reason	No embargo required	en
dc.check.type	No Embargo Required
dc.contributor.advisor	Moore, Thomas F.	en
dc.contributor.author	O'Riordan, Ronan T.
dc.contributor.funder	Health Research Board	en
dc.date.accessioned	2015-08-31T13:26:29Z
dc.date.available	2015-08-31T13:26:29Z
dc.date.issued	2014
dc.date.submitted	2014
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.description.status	Not peer reviewed	en
dc.description.version	Accepted Version
dc.format.mimetype	application/pdf	en
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.identifier.uri	https://hdl.handle.net/10468/1952
dc.language.iso	en	en
dc.publisher	University College Cork	en
dc.rights	© 2014, Ronan T. O'Riordan.	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	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.thesis.opt-out	false
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
ucc.workflow.supervisor	t.moore@ucc.ie