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Am J Physiol Lung Cell Mol Physiol (October 19, 2001). doi:10.1152/ajplung.00400.2000
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Articles in PresS, published online ahead of print October 19, 2001
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00400.2000
Submitted on November 22, 2000
Accepted on October 11, 2001

Thyroid Hormone Affects Embryonic Mouse Lung Branching Morphogenesis and Cellular Differentiation

Kwanchai Archavachotikul1, Teriggi J Ciccone1, Mala R Chinoy2, Heber C Nielsen1, and MaryAnn V Volpe1*

1 Department of Pediatrics, New England Medical Center, Tufts University School of Medicine, Boston, MA, USA
2 Lung Development Research Program, Department of Surgery, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA, USA

* To whom correspondence should be addressed. E-mail: mvolpe1{at}lifespan.org.

Although thyroid hormone (T3) influences epithelial cell differentiation during late fetal lung development, its effects on early lung morphogenesis are unknown. We hypothesized that T3 would alter embryonic lung airway branching and temporal-spatial differentiation of the lung epithelium and mesenchyme. Gestational day 11.5 embryonic mouse lungs were cultured for 72 hours in BGJb serum-free medium without or with added T3 (0.2, 2.0, 10.0, or 100 nM). Evaluation of terminal bud counts showed a dose- and time-dependent decrease in branching morphogenesis. Cell proliferation was also significantly decreased with higher doses of T3 . Morphometric analysis of lung histology showed that T3 caused a dose-dependent decrease in mesenchyme and increase in cuboidal epithelia and airway space. Immunocytochemistry showed that with T3 treatment, Nkx2.1 and SP-C proteins became progressively localized to cuboidal epithelial cells and mesenchymal expression of Hoxb-5 was reduced, a pattern resembling late fetal lung development. We conclude that exogenous T3 treatment during early lung development accelerated epithelial and mesenchymal cell differentiation at the expense of premature reduction in new branch formation and lung growth.




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