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Am J Physiol Lung Cell Mol Physiol 279: L1066-L1074, 2000;
1040-0605/00 $5.00
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Vol. 279, Issue 6, L1066-L1074, December 2000

Temporal/spatial expression of nuclear receptor coactivators in the mouse lung

Angela Naltner, Susan Wert, Jeffrey A. Whitsett, and Cong Yan

Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039

Our laboratory has previously demonstrated that retinoic acid nuclear receptor, thyroid transcription factor-1 (TTF-1), and nuclear receptor coactivators such as cAMP response element binding protein (CREB) binding protein (CBP)/p300 and steroid receptor coactivator-1 (SRC-1) form an enhanceosome on the 5'-enhancer region of the human surfactant protein B gene. Immunohistochemistry was used to identify cells that coexpressed CBP/p300, SRC-1, retinoid X receptor, and TTF-1 in the developing and mature lung. CBP/p300 and SRC-1 were expressed in the adult mouse lung, CBP and p300 being present in both alveolar type I and type II epithelial cells and SRC-1 and TTF-1 being restricted to type II epithelial cells. CBP/p300, SRC-1, and TTF-1 were readily detected in the nuclei of developing respiratory epithelial tubules in fetal mice from embryonic days 10 to 18. CBP/p300 and SRC-1 were also detected in developing mesenchymal cells. These coactivators were coexpressed with TTF-1 and SP-B in human pulmonary adenocarcinoma cells (H441 cells) in vitro. Interaction assays with a two-hybrid reporter analysis demonstrated direct interactions among TTF-1, SRC-1, and CBP/p300 in H441 cells. These findings support a role for retinoic acid receptor and nuclear receptor coactivators in the regulation of SP-B gene expression in the respiratory epithelium.

thyroid transcription factor-1; steroid receptor coactivator-1; cyclic adenosine 5'-monophosphate response element binding protein binding protein/p300; surfactant protein B; lung development


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