PDGF-AA and its receptor influence early lung branching via an epithelial-mesenchymal interaction.
The biological role of platelet-derived growth factor (PDGF)-AA in lung morphogenesis was investigated by incubating embryonic lung explants with phosphorothioate antisense PDGF-A oligonucleotides, which decreased PDGF-AA but not PDGF-BB protein content. Antisense PDGF-A oligonucleotides inhibited DNA synthesis. This inhibitory effect of antisense PDGF-A was reversed by the addition of exogenous PDGF-AA but not PDGF-BB. Morphometric analyses of antisense-treated cultures showed a significant reduction in lung size. The number of terminal buds of the lung explants was significantly decreased by antisense PDGF-A oligonucleotides. PDGF-AA but not PDGF-BB attenuated the inhibitory effect of antisense PDGF-A on early lung branching. Sense PDGF-A had no effect on DNA synthesis and early lung branching. Reverse transcriptase-polymerase chain reaction analysis revealed PDGF-A mRNA expression in the epithelial component of the embryonic lung, while message for PDGF alpha-receptor was expressed in the mesenchyme. Incubation of explants with neutralizing PDGF-AA antibodies also reduced DNA synthesis and early branching morphogenesis. We conclude that PDGF-AA and its receptor represent an important epithelial-mesenchymal interaction which plays a critical role in early lung branching morphogenesis.
Souza
P
P
Neonatal Research Division, Hospital for Sick Children Research Institute, University of Toronto, Ontario, Canada.
Kuliszewski
M
M
Wang
J
J
Tseu
I
I
Tanswell
A K
AK
Post
M
M
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000502:physiology; D015151:Immunoblotting; D008168:Lung / Q000196:embryology*; D008648:Mesoderm / Q000502:physiology; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology*
D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D004247:DNA; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor