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Department of Pediatrics and Obstetrics and Gynecology, Harbor-University of California Los Angeles Research and Education Institute, Torrance, California 90502
Developing rat
lung lipofibroblasts express leptin beginning on embryonic day (E) 17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed
mutually exclusively by fetal lung fibroblasts and type II cells,
suggesting a paracrine signaling "loop." This hypothesized
mechanism is supported by the following experimental data:
1) leptin stimulates the de novo synthesis of surfactant
phospholipid by both fetal rat type II cells (400% · 100 ng
1 · ml1 · 24 h1) and adult human airway epithelial cells
(85% · 100 ng1 · 24 h1);
2) leptin is secreted by lipofibroblasts in amounts that
stimulate type II cell surfactant phospholipid synthesis in vitro;
3) epithelial cell secretions such as parathyroid
hormone-related protein (PTHrP), PGE2, and dexamethasone
stimulate leptin expression by fetal rat lung fibroblasts;
4) PTHrP or leptin stimulate the de novo synthesis of
surfactant phospholipid (2- to 2.5-fold/24 h) and the expression of
surfactant protein B (SP-B; >25-fold/24 h) by fetal rat lung explants,
an effect that is blocked by a leptin antibody; and 5) a
PTHrP receptor antagonist inhibits the expression of leptin mRNA by
explants but does not inhibit leptin stimulation of surfactant phospholipid or SP-B expression, indicating that PTHrP paracrine stimulation of type II cell maturation requires leptin expression by
lipofibroblasts. This is the first demonstration of a paracrine loop
that functionally cooperates to induce alveolar acinar lung development.
lung development; surfactant; type II cell; lipofibroblast
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