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Title page for ETD etd-08192013-174125

Type of Document Dissertation
Author Carver, Billy Joe
Author's Email Address billy.carver@gmail.com
URN etd-08192013-174125
Title NF-κB interacts with SP3 to limit SP1-mediated FGF-10 expression in the developing fetal lung
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Mark de Caestecker Committee Chair
Chin Chiang Committee Member
Christopher Wright Committee Member
Lawrence Prince Committee Member
Timothy Blackwell Committee Member
  • inflammation
  • developmental biology
  • branching morphogenesis
  • NF-kappaB
  • mesenchymal cells
  • lung development
Date of Defense 2013-07-15
Availability unrestricted
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.
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