KGF and FGF-10 stimulate liquid secretion in human fetal lung

Area of Science:

• Pulmonary Medicine
• Developmental Biology
• Molecular Endocrinology

Background:

• Fetal lung liquid secretion is crucial for normal lung growth.
• Keratinocyte growth factor (KGF) and fibroblast growth factor 10 (FGF-10) are known to stimulate liquid secretion in murine models.
• The regulatory factors for human fetal lung liquid secretion are not well understood.

Purpose of the Study:

• To investigate the role of KGF and FGF-10 in stimulating human fetal lung liquid secretion.
• To examine the effects of KGF on transepithelial potential difference in human fetal lung explants.
• To determine the regulation of KGF and its receptor mRNA expression by cAMP and IL-6 in human fetal lung.

Main Methods:

• Human first-trimester fetal lung explants were treated with varying concentrations of KGF and FGF-10.
• Transepithelial potential difference was measured in response to KGF.
• Ribonuclease protection assays were used to quantify KGF and KGF receptor mRNA expression after stimulation with cAMP and IL-6.

Main Results:

• KGF and FGF-10 induced dose-dependent increases in intraluminal volume in human fetal lung explants.
• Long-term KGF exposure (60 h) led to depolarization of transepithelial potential difference.
• Both cAMP and IL-6 significantly increased KGF mRNA expression but not KGF receptor mRNA expression over 48 hours.

Conclusions:

• KGF and FGF-10 are potent stimulators of liquid secretion in the human fetal lung.
• cAMP-stimulated liquid secretion may be partly mediated by the induction of KGF expression.
• KGF and FGF-10 are likely important paracrine factors regulating human fetal lung development.