Abstract

The investigator proposes to assess the effect of RA, VitD, analogs, and dexamethasone individually or in combination on cell proliferation and expression of PDGFs and their receptors during lung development in vitro (Aim 1) and in vivo (Aim 2). This will include an evaluation of the effect of these treatments on alveolar formation and on lung function (Aim 2). Then, an analysis of the mechanisms regulating PDGF expression will be performed, aiming to characterize cis and trans elements potentially important on mediating transcriptional activation of the PDGF-A chain promoter during lung development (Aims 3 and 4).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL062877-03
Application #
6527361
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Berberich, Mary Anne
Project Start
2000-09-29
Project End
2004-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
3
Fiscal Year
2002
Total Cost
$228,859
Indirect Cost

  Institution

Name
University of Kentucky
Department
Pharmacology
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506

  Publications

Mishra, A; Ormerod, A K; Cibull, M L et al. (2009) PDGF-A promoter and enhancer elements provide efficient and selective antineoplastic gene therapy in multiple cancer types. Cancer Gene Ther 16:298-309
Ormerod, Angela K; Xing, Zhenlan; Pedigo, Nancy G et al. (2008) The calcitriol analogue EB1089 impairs alveolarization and induces localized regions of increased fibroblast density in neonatal rat lung. Exp Lung Res 34:155-82
Pedigo, Nancy G; Zhang, Hongxing; Mishra, Anjali et al. (2007) Retinoic acid inducibility of the human PDGF-a gene is mediated by 5'-distal DNA motifs that overlap with basal enhancer and vitamin D response elements. Gene Expr 14:1-12
Ma, Deqin; Nutt, Catherine L; Shanehsaz, Piam et al. (2005) Autocrine platelet-derived growth factor-dependent gene expression in glioblastoma cells is mediated largely by activation of the transcription factor sterol regulatory element binding protein and is associated with altered genotype and patient survival i Cancer Res 65:5523-34
Pedigo, Nancy G; Zhang, Hongxing; Bruno, Maria E C et al. (2005) A 5'-distal enhanceosome in the PDGF-A gene is activated in choriocarcinoma cells via ligand-independent binding of vitamin D receptor and constitutive jun kinase signaling. Oncogene 24:2654-66
Zhang, Qingbei; Pedigo, Nancy; Shenoy, Satyendra et al. (2005) Puralpha activates PDGF-A gene transcription via interactions with a G-rich, single-stranded region of the promoter. Gene 348:25-32
Kaetzel, David M (2003) Transcription of the platelet-derived growth factor A-chain gene. Cytokine Growth Factor Rev 14:427-46
Pedigo, Nancy; Zhang, Hongxing; Koszewski, Nicholas J et al. (2003) A 5'-distal element mediates vitamin D-inducibility of PDGF-A gene transcription. Growth Factors 21:151-60
Srinivasan, Ganesh; Bruce, Eugene N; Houtz, Pamela K et al. (2002) Dexamethasone-induced changes in lung function are not prevented by concomitant treatment with retinoic acid. Am J Physiol Lung Cell Mol Physiol 283:L275-87