Different roles for PDGF-alpha and -beta receptors in embryonic lung development

Area of Science:

• Developmental Biology
• Cell Signaling
• Molecular Biology

Background:

• Platelet-derived growth factor (PDGF) is crucial for normal lung development.
• PDGF-AA and PDGF-BB homodimers are present in embryonic rat lungs.
• PDGF-AA influences embryonic lung branching, while PDGF-BB affects embryonic lung growth.

Purpose of the Study:

• Investigate the roles of PDGF alpha- and beta-receptors in early embryonic rat lung development.
• Determine the specific signaling pathways mediated by each PDGF receptor isoform.

Main Methods:

• Reverse-transcriptase-polymerase chain reaction (RT-PCR) to analyze receptor mRNA expression in lung mesenchyme.
• Phosphorothioate antisense oligonucleotides to reduce PDGF receptor mRNA expression and signaling.
• Treatment of embryonic lung explants with antisense and sense oligonucleotides for alpha and beta receptors.
• Assessment of lung growth and branching following receptor inhibition and growth factor addition.

Main Results:

• Both PDGF alpha- and beta-receptor mRNAs are primarily expressed in embryonic lung mesenchyme.
• Antisense oligonucleotides targeting PDGF receptors reduced receptor mRNA and tyrosine phosphorylation.
• Inhibition of the beta-receptor impaired lung growth, but not branching; this effect was reversible with PDGF-AA or PDGF-BB.
• Inhibition of the alpha-receptor reduced both lung growth and branching; PDGF-BB partially rescued growth but not branching.

Conclusions:

• PDGF-BB signaling through both alpha and beta receptors promotes embryonic lung growth.
• PDGF-AA signaling specifically through the alpha receptor is essential for embryonic lung branching.
• The alpha receptor plays a unique role in lung branching that cannot be substituted by the beta receptor.