TGF-beta1-Dependent Regulation of miR-21 in Bovine Fetal Fibroblasts

dc.contributor.advisorLaMarre, Jonathan
dc.contributor.authorAhmed, Syed Moez
dc.date.accessioned2016-10-24T19:13:32Z
dc.date.available2017-09-28T05:00:17Z
dc.date.copyright2016-09
dc.date.created2016-09-28
dc.date.issued2016-10-24
dc.degree.departmentDepartment of Biomedical Sciencesen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameMaster of Scienceen_US
dc.degree.programmeBiomedical Sciencesen_US
dc.description.abstractThe TGF-β/SMAD signaling pathway has been previously implicated in the induction of miR-21 expression, with studies offering conflicting data implicating transcription or expedited processing as the primary mechanism of induction. Real-time qPCR revealed significant induction of both primary-miR-21 (pri-miR-21) and mature miR-21 following TGF-β1 treatment. Luciferase reporter constructs under the control of the bovine pri-miR-21 promoter demonstrated strong TGF-β responsiveness that was lost when SMAD binding sites were ablated. To identify potential roles for the induced miR-21, we examined cellular expression of PDCD4. TGF-β1 strongly suppressed PDCD4 expression, which was, in turn, highly correlated with a significant increase in cellular viability and loss of cleaved caspase-3. Studies with miR- 21 antagonists demonstrated that these downstream effects of TGF-β1 are miR-21 dependent. Taken together, these studies show that TGF-β1 activated SMAD 2/3 proteins mediate the transcription of pri-miR-21 transcript in bovine fibroblasts in vitro which then suppress apoptosis through altered PDCD4 expression.en_US
dc.identifier.urihttp://hdl.handle.net/10214/10064
dc.language.isoenen_US
dc.publisherUniversity of Guelphen_US
dc.rightsAttribution-NonCommercial-NoDerivs 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/ca/*
dc.subjectTGF-beta 1-dependent regulationen_US
dc.subjectmiR-21en_US
dc.subjectBovine fetal fibroblastsen_US
dc.subjectAltered PDCD4 expressionen_US
dc.subjectCellular viabilityen_US
dc.titleTGF-beta1-Dependent Regulation of miR-21 in Bovine Fetal Fibroblastsen_US
dc.typeThesisen_US

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