Zeb2: A novel regulator of cardiac fibroblast to myofibroblast transition

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dc.contributor.authorJahan, Fahmida
dc.contributor.examiningcommitteeNachtigal, Mark (Biochemistry and Medical Genetics) Dixon, Ian (Physiology and Pathophysiology)en_US
dc.contributor.supervisorWigle, Jeffrey (Biochemistry and Medical Genetics)en_US
dc.date.accessioned2016-01-15T15:38:22Z
dc.date.available2016-01-15T15:38:22Z
dc.date.issued2014-01en_US
dc.date.issued2015-04en_US
dc.date.issued2014-04en_US
dc.degree.disciplineBiochemistry and Medical Geneticsen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractCardiac fibroblast to myofibroblast phenoconversion is a critical step during the development of cardiac fibrosis. Myofibroblasts chronically remodel extracellular matrix that results in myocardial stiffening, cardiac dysfunction and eventually heart failure. Previously we showed that Meox2, a homeobox transcription factor, can inhibit myofibroblast phenoconversion. Here we show that Zeb2, a repressor of Meox2, plays a crucial role during this phenoconversion process. Zeb2 overexpression significantly upregulates the expression of three key myofibroblast markers: α-SMA, SMemb and ED-A fibronectin in primary rat cardiac myofibroblast. We show that Zeb2 is highly expressed in myofibroblast nuclei whereas it is minimally expressed in fibroblast nuclei. Zeb2 overexpression in myofibroblasts results in a less migratory and more contractile mature myofibroblast phenotype. Moreover, Zeb2 overexpression represses Meox2 expression in endothelial cells. Thus, the current study enhances our understanding of the mechanism behind myofibroblast phenoconversion and provides a basis for developing Zeb2-based novel anti-fibrotic drug in the future.en_US
dc.description.noteFebruary 2016en_US
dc.identifier.citationCunnington, R.H., et al., The Ski-Zeb2-Meox2 pathway provides a novel mechanism for regulation of the cardiac myofibroblast phenotype. J Cell Sci, 2014. 127(Pt 1): p. 40-9.en_US
dc.identifier.citationJahan, F., et al., Control of Cardiac Fibroblast Phenotype by the Meox2/Zeb2 Signalling Switch. The FASEB Journal,2014. vol. 28 no. 1 Supplement LB47en_US
dc.identifier.citationJahan, F., et al., Zeb2: A novel regulator of cardiac fibroblast to myofibroblast transition. The FASEB Journal, 2015. vol. 29 no. 1 Supplement 556.1en_US
dc.identifier.urihttp://hdl.handle.net/1993/31090
dc.language.isoengen_US
dc.publisherCompany of biologists Ltd.en_US
dc.publisherFederation of American Societies for Experimental Biologyen_US
dc.rightsopen accessen_US
dc.subjectZeb2en_US
dc.subjectMeox2en_US
dc.subjectCardiac fibroblasten_US
dc.subjectMyofibroblasten_US
dc.subjectPhenoconversionen_US
dc.subjectCardiac fibrosisen_US
dc.titleZeb2: A novel regulator of cardiac fibroblast to myofibroblast transitionen_US
dc.typemaster thesisen_US
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