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Am J Physiol Lung Cell Mol Physiol 290: L250-L258, 2006. First published September 2, 2005; doi:10.1152/ajplung.00244.2005
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VDUP1: a potential mediator of expansion-induced lung growth and epithelial cell differentiation in the ovine fetus

C. E. Filby, S. B. Hooper, F. Sozo, V. A. Zahra, S. J. Flecknoe, and M. J. Wallace

Fetal and Neonatal Research Group, Department of Physiology, Monash University, Victoria, 3800, Australia

Submitted 3 June 2005 ; accepted in final form 31 August 2005

The degree of fetal lung expansion is a critical determinant of fetal lung growth and alveolar epithelial cell (AEC) differentiation, although the mechanisms involved are unknown. As VDUP1 (vitamin D3-upregulated protein 1) can modulate cell proliferation, can induce cell differentiation, and is highly expressed in the lung, we have investigated the effects of fetal lung expansion on VDUP1 expression and its relationship to expansion-induced fetal lung growth and AEC differentiation in fetal sheep. Alterations in fetal lung expansion caused profound changes in VDUP1 mRNA levels in lung tissue. Increased fetal lung expansion significantly reduced VDUP1 mRNA levels from 100 ± 8% in control fetuses to 37 ± 4, 46 ± 4, and 45 ± 9% of control values at 2, 4, and 10 days of increased fetal lung expansion, respectively. Reduced fetal lung expansion increased VDUP1 mRNA levels from 100 ± 16% in control fetuses to 162 ± 16% of control values after 7 days. VDUP1 was localized to airway epithelium in small bronchioles, AECs, and some mesenchymal cells. Its expression was inversely correlated with cell proliferation during normal lung development (R2 = 0.972, P < 0.002) as well as in response to alterations in fetal lung expansion (R2 = 0.956, P < 0.001) and was positively correlated with SP-B expression during normal lung development (R2 = 0.803, P < 0.0001) and following altered lung expansion (R2 = 0.817, P < 0.001). We suggest that VDUP1 may be an important mediator of expansion-induced lung cell proliferation and AEC differentiation in the developing lung.

vitamin D3-upregulated protein 1; fetal lung development; lung expansion; cell proliferation; surfactant protein B



Address for reprint requests and other correspondence: C. E. Filby, Dept. of Physiology, Bldg. 13F, Monash Univ., Vic 3800, Australia (e-mail: Caitlin.Filby{at}med.monash.edu.au)




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F. Sozo, S. B. Hooper, and M. J. Wallace
Thrombospondin-1 expression and localization in the developing ovine lung
J. Physiol., October 15, 2007; 584(2): 625 - 635.
[Abstract] [Full Text] [PDF]




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