1,25-Dihydroxyvitamin D3 and fetal lung maturation:: immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1,6 bisphosphatase

Lung maturation before birth includes type 11 pneumocyte differentiation with progressive disappearance of glycogen content and onset of surfactant synthesis. We have shown previously that 1,25-(OH)2D3 increases surfactant synthesis and secretion by type 11 cells and decreases their glycogen content in fetal rat lung explants. Recently, the gene coding fructose 1,6 bisphosphatase (F1,6BP), a regulatory enzyme of gluconeogenesis, has been identified in type 11 cells and its promoter bears a Vitamin D response element. Present results show: 1. The coexistence of type 11 cells at different stages of maturation. in rat fetal lung on day 21 of gestation (electron microscopy), and the association between maturation of type 11 cells and disappearance of their glycogen content. 2. The immunogold labeling of all type 11 cells when using the 9A7g VDR-antibody, with significantly more abundant gold particles in cells exhibiting an intermediate glycogen content. 3. The expression of F 1,6BP mRNA in a human type 11 cell line (NCI-H441) and the increase of this expression after 18 h incubation with 1,25-(OH)2D3 (10(-8) M). These results bring further evidence for a physiological role of 1,25-(OH)2D3 during type 11 pneumocyte maturation. Activation of F1,6BP may participate to the 1,25-(OH)2D3 action on surfactant synthesis via the gluconeogenesis pathway. (C) 2004 Elsevier Ltd. All rights reserved.