Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF-I double deficient embryos

Dev Dyn. 2006 Aug;235(8):2040-50. doi: 10.1002/dvdy.20842.


Previous studies on double deficient mice for leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) reported that they died of respiratory failure, with abnormal lung histology and altered expression of pulmonary markers. Here we analyzed prenatal Lif/Igf-I double mutant mouse embryos to characterize LIF and IGF-I cooperative roles in distal lung epithelium and vascular maturation. Lungs of IGF-I-deficient embryos displayed a higher proportion of type II pneumocytes, less differentiated type I pneumocytes, and failure in alveolar capillary remodeling compared to wild type and LIF-deficient mice. Lif/Igf-I double knockout lungs showed aggravated pulmonary hypoplasia, lower airway volume, increased proliferation, and elevated levels of ERK1/2 activation. In addition, their alveoli were collapsed and lined by type II cells. The differentiation of type I cells barely occurred and capillaries remained in the abundant mesenchyme. These results indicate that LIF collaborates with IGF-I in lung alveolar epithelium and vascular maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation*
  • Cell Proliferation
  • Epithelium / blood supply
  • Epithelium / embryology
  • Epithelium / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Developmental
  • Insulin-Like Growth Factor I / deficiency*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Interleukin-6 / deficiency*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Leukemia Inhibitory Factor
  • Lung / blood supply*
  • Lung / cytology
  • Lung / embryology*
  • Lung / metabolism
  • Mice
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Messenger / genetics


  • Biomarkers
  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Extracellular Signal-Regulated MAP Kinases