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dc.contributor.authorAKTAR, Ren_US
dc.contributor.editorBlackshaw, Aen_US
dc.contributor.editorAziz, Qen_US
dc.descriptionFunding via Bowel and Cancer Research
dc.descriptionFunding via Bowel and Cancer Researchen_US
dc.description.abstractTenascin X (TNX) is a matricellular protein involved in regulating cellular functions by interacting with other extracellular matrix (ECM) proteins within the cell matrix and has anti-adhesive properties evidenced in tumours and wound healing. TNX is the only member of the tenascin family that is lost in Joint Hypermobility Syndrome (JHS) and exerts a crucial architectural function. Of importance, TNX deficient and JHS patients have gastrointestinal (GI) dysfunction. Despite this association no study has described the role of TNX in the GI tract. Thus, the aim of this thesis was to characterise the expression of TNX in the stomach and colon in mouse and human tissue. Second, we aimed to elucidate the functional role of TNX using TNX knockout (TNX KO) mice. Expression studies revealed TNX in vagal afferent endings in the mouse, and myenteric cell bodies in human stomach. In colon, TNX strongly associated with cholinergic submucous and myenteric neurons in both species, however, was not found in CGRP positive fibres. Cell bodies in nodose ganglia, dorsal root ganglia, ventral and dorsal horn were also TNX positive. Functional studies in stomach, using single fibre electrophysiology showed TNX KO mice had increased vagal afferent mechanoreceptor sensitivity. Octanoic acid breath test revealed rapid gastric emptying in TNX KO. Colonic manometry showed the amplitude and frequency of colonic contractions were reduced in TNX KO mice, particularly in the distal colon. Ussing chamber studies measuring changes in ion flux (indirect measure of secretion) showed no major difference between TNX KO and wild type (WT) mice. The specific localisation of TNX with neuronal structures in the gut is shown here for the first time suggesting that TNX is more than just an architectural protein. Indeed, its role in specific GI functions supports this observation and provides a mechanism for GI symptoms in JHS.en_US
dc.description.sponsorshipBowel and Cancer Researchen_US
dc.subjectTenascin Xen_US
dc.subjectgastrointestinal dysfunction.en_US
dc.subjectJoint Hypermobility Syndromeen_US
dc.title1 Multiple roles for the extracelllular matrix protein Tenascin-X in nerve gut functionen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
pubs.notesNo embargoen_US

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  • Theses [2793]
    Theses Awarded by Queen Mary University of London

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