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Fetal lung epithelial cells express receptors for platelet-derived growth factor
I Caniggia1, J Liu, R Han
1Department of Paediatrics, Hospital for Sick Children Research Institute, Toronto, Canada.
Insights
Platelet-derived growth factor (PDGF) receptors are present on fetal rat lung epithelial cells, mediating mitogenic responses to all PDGF isoforms. Fibroblasts express only the beta-receptor, responding differently to PDGF stimulation.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Platelet-derived growth factor (PDGF) and similar molecules are implicated in fetal lung development.
- Previous research showed fetal lung epithelial cells are mitogenically responsive to PDGF, while fibroblasts increase glycosaminoglycan synthesis.
Purpose of the Study:
- To investigate the presence and characteristics of PDGF receptors in fetal rat lung cells.
- To identify specific PDGF isoforms and their effects on epithelial cells and fibroblasts.
Main Methods:
- Utilized Northern blot and protein analysis to detect PDGF receptors (alpha and beta).
- Assessed tyrosine kinase activity and receptor autophosphorylation upon PDGF isoform stimulation.
- Performed binding experiments using radiolabeled PDGF isoforms ([125I]PDGF-AA and [125I]-PDGF-BB).
Main Results:
- Fetal lung epithelial cells express both PDGF alpha- and beta-receptors, responding mitogenically to PDGF-AA, -AB, and -BB.
- All PDGF isoforms enhanced tyrosine kinase activity and autophosphorylation in epithelial cells.
- Fetal lung fibroblasts express only the PDGF beta-receptor, with PDGF-AB and -BB stimulating tyrosine kinase activity, and PDGF-BB promoting proliferation under specific conditions.
Conclusions:
- Fetal rat lung epithelial cells possess functional PDGF receptors (alpha and beta) that mediate mitogenic responses to various PDGF isoforms.
- Fetal lung fibroblasts exhibit distinct PDGF receptor expression (beta-receptor only) and signaling pathways.
- These findings clarify the specific cellular targets and signaling mechanisms of PDGF in fetal lung development.
Abstract:
There is increasing evidence to suggest that platelet-derived growth factor (PDGF) or PDGF-like molecules play a role in fetal lung morphogenesis. Our previous studies demonstrated that fetal lung epithelial cells respond mitogenically to exogenous PDGF, while fetal lung fibroblasts respond with increased glycosaminoglycan synthesis. To further study the target cells of PDGF in fetal rat lung, we investigated the presence and nature of PDGF receptors in fetal lung cells. Functional PDGF receptors were expressed on normal epithelial cells of fetal rat lung. All three isoforms of PDGF (AA, AB, and BB) were mitogenic for quiescent epithelial cells. Northern blot and protein analysis demonstrated the presence of PDGF alpha-receptor and PDGF beta-receptor. All isoforms of PDGF enhanced tyrosine kinase activity and stimulated receptor autophosphorylation. In contrast, fetal lung fibroblasts expressed only the PDGF beta-receptor. PDGF-AB and PDGF-BB, but not PDGF-AA, stimulated tyrosine kinase activity. No PDGF isoform was mitogenic for quiescent fibroblasts. However, PDGF-BB stimulated fibroblast proliferation on a collagen type I substratum in the presence of transferrin. Binding experiments with [125I]PDGF-AA and [125I]-PDGF-BB to epithelial cells and fibroblasts confirmed these observations.