dc.creator | Carver, Billy Joe | |
dc.date.accessioned | 2020-08-22T20:49:03Z | |
dc.date.available | 2014-09-18 | |
dc.date.issued | 2013-09-18 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-08192013-174125 | |
dc.identifier.uri | http://hdl.handle.net/1803/13944 | |
dc.description.abstract | Arrested lung development in preterm infants leads to bronchopulmonary dysplasia (BPD). Inflammation and NF-κB activation in the fetal lung inhibit airway morphogenesis and contribute to BPD. The mesenchymal growth factor FGF-10 is crucial for normal airway branching and is decreased in lungs of patients with BPD. I therefore hypothesized that when activated, NF-κB disrupts normal FGF-10 transcription. I discovered that FGF-10 is in fact downregulated by NF-κB activation, but in an indirect manner. Further analysis of the FGF-10 promoter revealed many sites consistent with regulation by Sp proteins. Experiments revealed that Sp1 and Sp3 also regulate FGF-10; Sp1 activates transcription, while Sp3 downregulates Sp1-mediated expression. I further discovered that Sp3 and the NF-κB dimer interact during FGF-10 suppression, suggesting that NF-κB recruits Sp3 to the FGF-10 promoter. This is a novel mechanism of gene regulation in the developing lung. | |
dc.format.mimetype | application/pdf | |
dc.subject | inflammation | |
dc.subject | developmental biology | |
dc.subject | branching morphogenesis | |
dc.subject | NF-kappaB | |
dc.subject | mesenchymal cells | |
dc.subject | lung development | |
dc.title | NF-κB interacts with SP3 to limit SP1-mediated FGF-10 expression in the developing fetal lung | |
dc.type | dissertation | |
dc.contributor.committeeMember | Lawrence Prince | |
dc.contributor.committeeMember | Christopher Wright | |
dc.contributor.committeeMember | Chin Chiang | |
dc.contributor.committeeMember | Timothy Blackwell | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2014-09-18 | |
local.embargo.lift | 2014-09-18 | |
dc.contributor.committeeChair | Mark de Caestecker | |