RGD Reference Report - Different roles for PDGF-alpha and -beta receptors in embryonic lung development. - Rat Genome Database

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

Authors: Souza, P  Tanswell, AK  Post, M 
Citation: Souza P, etal., Am J Respir Cell Mol Biol. 1996 Oct;15(4):551-62.
RGD ID: 11087558
Pubmed: (View Article at PubMed) PMID:8879189
DOI: Full-text: DOI:10.1165/ajrcmb.15.4.8879189

Platelet-derived growth factor (PDGF) is implicated in the process of normal lung development. We have previously shown the presence of PDGF-AA and BB homodimers in embryonic rat lung. Also, we reported that PDGF-AA is involved in embryonic lung branching, whereas PDGF-BB influences embryonic lung growth. PDGF isoforms bind with different affinities to two related receptors, denoted the PDGF alpha- and beta-receptors, respectively. The alpha-receptor binds both PDGF isoforms, whereas the beta-receptor binds only PDGF-BB. In the present study, we investigated the role of both receptors in early embryonic rat lung development. Reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that both PDGF alpha- and beta-receptor mRNAs are mainly expressed in the mesenchyme. Phosphorothioate antisense receptor oligonucleotides decreased PDGF receptor mRNA expression in early lung explants. PDGF-induced receptor tyrosine phosphorylation was also reduced by the antisense oligonucleotides. Incubation of embryonic lung explants with antisense beta-receptor oligonucleotides inhibited lung growth but not early lung branching. Neither growth nor branching were affected by sense beta-receptor oligonucleotides. The inhibitory effect of antisense beta-receptor oligonucleotides on embryonic lung growth was reversed by the addition of PDGF-BB or PDGF-AA, suggesting that the alpha-receptor can transduce similar mitogenic signals as the beta-receptor in early lung development. Antisense alpha-receptor oligonucleotides reduced both embryonic lung growth and branching. Sense alpha-receptor treatment had no effect on lung growth and branching. PDGF-BB but not PDGF-AA partially attenuated the inhibitory effect of antisense alpha-receptor oligonucleotides on lung growth. In contrast, PDGF-BB did not overcome the inhibitory effect on early lung branching, indicating that the beta-receptor cannot replace this biologic role of the alpha-receptor in early lung development. These data suggest that PDGF-BB stimulation of both receptors leads to lung growth, whereas PDGF-AA stimulation of the alpha-receptor induces transduction pathways that lead lung branching.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Pdgfra  (platelet derived growth factor receptor alpha)
Pdgfrb  (platelet derived growth factor receptor beta)


Additional Information