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Am J Physiol Lung Cell Mol Physiol 280: L695-L704, 2001;
1040-0605/01 $5.00
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Vol. 280, Issue 4, L695-L704, April 2001

Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury

Vladimir V. Kalinichenko, Lorena Lim, Brian Shin, and Robert H. Costa

Department of Molecular Genetics, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60607-7170

The forkhead box (Fox) proteins are a growing family of transcription factors that have important roles in cellular proliferation and differentiation and in organ morphogenesis. The Fox family members hepatocyte nuclear factor (HNF)-3beta (Foxa2) and HNF-3/forkhead homolog (HFH)-8 (FREAC-1, Foxf1) are expressed in adult pulmonary epithelial and mesenchymal cells, respectively, but these cells display only low expression levels of the proliferation-specific HFH-11B gene (Trident, Foxm1b). The regulation of these Fox transcription factors in response to acute lung injury, however, has yet to be determined. We report here on the use of butylated hydroxytoluene (BHT)-mediated lung injury to demonstrate that HFH-11 protein and RNA levels were markedly increased throughout the period of lung repair. The maximum levels of HFH-11 were observed by day 2 following BHT injury when both bronchiolar and alveolar epithelial cells were undergoing extensive proliferation. Although BHT lung injury did not alter epithelial cell expression of HNF-3beta , a 65% reduction in HFH-8 mRNA levels was observed during the period of mesenchymal cell proliferation. HFH-8-expressing cells were colocalized with platelet endothelial cell adhesion molecule-1-positive alveolar endothelial cells and with alpha -smooth muscle actin-positive peribronchiolar smooth muscle cells.

winged helix/forkhead box DNA binding domain; hepatocyte nuclear factor 3/forkhead homolog; alveolar endothelial cell; alveolar type II cell; bronchiolar epithelial cells.


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