PDGF-C controls proliferation and is down-regulated by retinoic acid in mouse embryonic palatal mesenchymal cells.
BACKGROUND
Platelet-derived growth factor C (PDGF-C) was recently identified as a member of the PDGF ligand family. Some observation suggests that PDGF-C could play an important role in palatogenesis highlighted by the Pdgfc(-/-) mouse with cleft palate, which led us to examine the mechanism of PDGF-C signaling in palatogenesis. It is well known that retinoic acid (RA) is a teratogen that can effectively induce cleft palate in the mouse. Due to the critical roles of PDGF-C and RA in cleft palate, the link between cleft palate induced by RA and loss of PDGF-C was investigated.


METHODS
Retarded mesenchymal proliferation is an important cause for cleft palate. To clarify the mechanism of PDGF-C in palatogenesis, we evaluated the effects of PDGF-C and anti-PDGF-C neutralizing antibody on proliferation activity in mouse embryonic palatal mesenchymal (MEPM) cells.


RESULTS
Briefly, our results show PDGF-C promotes proliferation, anti-PDGF-C antibody inhibits it in MEPM cells, and RA downregulates the PDGF-C expression both at the mRNA and protein levels.


CONCLUSIONS
These demonstrate that PDGF-C is a potent mitogen for MEPM cells, implying that inactivated PDGF-C by gene-targeting or reduced PDGF-C by RA may both cause inhibition of proliferation in palatal shelves, which might account for the pathogenesis of cleft palate in Pdgfc(-/-) mouse or RA-treated mouse. In conclusion, our results suggest that PDGF-C signaling is a new mechanism of cleft palate induced by RA.
Han
Jing
J
Department of Food Science and Nutrition, School of Public Health, Peking University, Beijing 100083, China.
Xiao
Ying
Y
Lin
Jiuxiang
J
Li
Yong
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D010159:Palate / Q000166:cytology* / Q000196:embryology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000633:toxicity*
D000906:Antibodies; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C411423:platelet-derived growth factor C; D014212:Tretinoin; D001973:Bromodeoxyuridine