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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.
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.

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CRRD Object Information
CRRD ID: 11087558
Created: 2016-06-02
Species: All species
Last Modified: 2016-06-02
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.