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Am J Physiol Lung Cell Mol Physiol 282: L359-L369, 2002. First published October 19, 2001; doi:10.1152/ajplung.00400.2000
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Vol. 282, Issue 3, L359-L369, March 2002

SPECIAL TOPIC
Pre- and Postnatal Lung Development, Maturation, and Plasticity
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, Division of Newborn Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111; and 2 Lung Development Research Program, Department of Surgery, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

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 h 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 surfactant protein SP-C proteins became progressively localized to cuboidal epithelial cells and mesenchymal expression of Hoxb5 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.

triiodothyronine; lung development; Nkx2.1; Hoxb5; surfactant protein-C


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