Han Jing, Xiao Ying, Lin Jiuxiang, Li Yong
Department of Food Science and Nutrition, School of Public Health, Peking University, Beijing 100083, China.
Birth Defects Res B Dev Reprod Toxicol. 2006 Oct;77(5):438-44. doi: 10.1002/bdrb.20094.
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.
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.
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.
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.
血小板源性生长因子C（PDGF-C）最近被鉴定为PDGF配体家族的一员。一些观察结果表明，PDGF-C可能在腭发育过程中发挥重要作用，腭裂的Pdgfc(-/-)小鼠就突出了这一点，这促使我们研究PDGF-C信号在腭发育中的机制。众所周知，视黄酸（RA）是一种致畸剂，可有效诱导小鼠腭裂。由于PDGF-C和RA在腭裂中起关键作用，因此研究了RA诱导的腭裂与PDGF-C缺失之间的联系。
间充质增殖迟缓是腭裂的一个重要原因。为了阐明PDGF-C在腭发育中的机制，我们评估了PDGF-C和抗PDGF-C中和抗体对小鼠胚胎腭间充质（MEPM）细胞增殖活性的影响。
简而言之，我们的结果表明，PDGF-C促进增殖，抗PDGF-C抗体在MEPM细胞中抑制增殖，并且RA在mRNA和蛋白质水平上均下调PDGF-C表达。
这些结果表明，PDGF-C是MEPM细胞的一种有效的促有丝分裂原，这意味着通过基因靶向使PDGF-C失活或通过RA降低PDGF-C水平都可能导致腭突增殖受到抑制，这可能解释了Pdgfc(-/-)小鼠或经RA处理的小鼠发生腭裂的发病机制。总之，我们的结果表明，PDGF-C信号是RA诱导腭裂的一种新机制。
