A549 cells can be induced by Foxp3 to express SPC in the presence of Nkx2.1. SPC is entirely alveolar-specific in the developed lung, whereas SPA and CC10 are expressed in the bronchiolar epithelium Club cells (also called Clara cells). Furthermore, SPC is completely lung-specific, whereas both SPA and CC10 are expressed in extra pulmonary tissues as well.
Reference: Life Sci. 2010 Jul 3;87(1-2):17-25. doi: 10.1016/j.lfs.2010.05.009. Epub 2010. The mouse forkhead gene Foxp2 modulates expression of the lung genes.
Yang Z1, Hikosaka K, Sharkar MT, Tamakoshi T, Chandra A, Wang B, Itakura T, Xue X, Uezato T, Kimura W, Miura N.
Abstract: AIMS: Foxp2 is expressed in the lung during mouse development. A monoclonal anti-mouse Foxp2 antibody was created to determine the expression pattern in the developing lung. Next, transcriptional control of two lung genes, CC10 and surfactant protein C (SPC) genes, by Foxp2 was investigated in H441 and A549 cells. Thirdly, expression patterns of Foxp2 and Foxf2 were compared in the developing lung. Finally, Foxp2 expression was determined in the Foxf2-null mice. MAIN METHODS:
Immunohistochemical staining and in situ hybridization were applied to the sections of lungs in the developing embryos.
KEY FINDINGS:
Monoclonal anti-Foxp2 antibody demonstrated that Foxp2 was expressed in the bronchial epithelium at E10.5 and its expression became restricted to the distal portion of the elongating bronchiolar epithelium and finally to type II alveolar epithelial cells around birth and in the adult. Foxp2 activated the SPC gene promoter in the presence of Nkx2.1 in A549 cells while it repressed the CC10 gene promoter in H441 cells. Next, the expression domains of the Foxp2 and Foxf2 were found to be exclusive in the lung. Finally, the expression of Foxp2 did not change in the lung of Foxf2-null mice.
SIGNIFICANCE:
The Foxp2 protein is expressed in the growing distal edge of airway epithelium. When the bronchiolus elongates, Foxp2 suppresses CC10 expression. When the lung alveolus is formed, Foxp2 modulates the Nkx2.1-mediated SPC expression in type II alveolar cells. Foxp2 and Foxf2 independently play distinct roles in the alveoli and the mesenchyme, respectively.
Copyright 2010 Elsevier Inc. All rights reserved.
PMID: 20553735 [PubMed - indexed for MEDLINE]
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