Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 282, Issue 3, Pages L405-L410Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.2002.282.3.L405
Keywords
lung development; surfactant; type II cell; lipofibroblast
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL075405, R01HL055268] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL075405, R01 HL055268-12, HL-55268, R01 HL055268, R01 HL075405-04] Funding Source: Medline
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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),ml(-1).24 h(-1)) and adult human airway epithelial cells (85%.100 ng(-1).24 h(-1)); 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), PGE(2), 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.
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