Effects of premature weaning and diet on lung growth and appearance of adenylate cyclase activator in rat lung

Nijjar, M. S.; Hatch, Grant M.

doi:10.1007/bf00238438

Cited by 1 publication

(1 citation statement)

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“…LW/BW ratio in Foxa1 Ϫ/Ϫ mice was similar to that in Foxa1 ϩ/ϩ mice. Previous studies showed that caloric restriction causes a delay in lung morphogenesis, with more prominent effects observed during phases of growth and differentiation (23,30,35). Although surfactant phospholipid content was reduced, surfactant composition was normal in lungs of calorie-deprived animals before birth or during adulthood (8,23).…”

Section: Foxa1mentioning

confidence: 98%

Stage-specific regulation of respiratory epithelial cell differentiation by Foxa1

Besnard¹,

Wert²,

Kaestner³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Foxa1 is a member of the winged helix family of transcription factors that is expressed in epithelial cells of the conducting airways and in alveolar type II cells of the lung. To determine the role of Foxa1 during lung morphogenesis, histology and gene expression were assessed in lungs from Foxa1−/− gene-targeted mice from embryonic day (E) 16.5 to postnatal day (PN) 13. Deletion of Foxa1 perturbed maturation of the respiratory epithelium at precise times during lung morphogenesis. While dilatation of peripheral lung saccules was delayed in Foxa1−/− mice at E16.5, sacculation was unperturbed later in development (E17.5–E18.5). At PN5, alveolarization was markedly delayed in Foxa1−/− mice; however, by PN13 lung histology was comparable to wild-type controls. Clara cell secretory protein (CCSP), prosurfactant protein (SP)-C, and SP-B protein content and immunostaining were decreased in Foxa1−/− mice between E16.5 and E18.5 but normalized after birth. Timing and sites of expression of thyroid transcription factor-1, Foxj1, and β-tubulin were unaltered in lungs of Foxa1−/− mice. In vitro, Foxa1 regulated the activity of CCSP and SP-A, SP-B, SP-C, and SP-D promoters as assessed by luciferase reporter assays in HeLa, H441, and MLE15 cells. Although Foxa1 regulates respiratory epithelial differentiation and structural maturation of the lung at precise developmental periods, the delay in maturation is subsequently compensated at times to enable respiratory function and restore normal lung structure after birth.

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