Platelet-derived growth factor receptor regulates salivary gland morphogenesis via fibroblast growth factor expression
Platelet-derived growth factor receptor regulates salivary gland morphogenesis via fibroblast growth factor expression
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DOI：
10.1074/jbc.m710308200
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发表时间：
2008-08-22
影响因子：
4.8
通讯作者：
Fukumoto, Satoshi
中科院分区：
文献类型：
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作者：
Yamamoto, Shinya;Fukumoto, Emiko;Fukumoto, Satoshi
上皮细胞和间充质细胞之间的相互作用参与了唾液腺的形态发生。Wnt 1-Cre/R26 R小鼠的下颌下腺（SMG）显示间充质阳性，而上皮细胞为β-半乳糖苷酶阴性，表明大多数间充质细胞来源于颅神经嵴细胞。血小板衍生生长因子（PDGF）受体α是神经嵴衍生细胞的标志物之一。在这项研究中，我们分析了PDGFs及其受体在小鼠SMGs形态发生中的作用。PDGF-A显示在SMG上皮中表达，而PDGF-B、PDGFR α和PDGFR β在间充质中表达。外源性PDGF-AA和-BB在SMG器官培养物中表现出增加的分支和上皮细胞增殖水平，尽管它们的受体被发现在间充质中表达。相比之下，短干扰RNA的Pdgfa和-B以及中和抗体的PDGF-AB和-BB显示减少分支。PDGF-AA诱导成纤维细胞生长因子基因Fgf 3和-7的表达，PDGF-BB诱导Fgf 1、-3、-7和-10的表达，而Pdgfa和Pdgfb的短干扰RNA抑制Fgf 3、-7和-10的表达，表明PDGFs调节SMG间充质中Fgf基因的表达。PDGF受体抑制剂AG-17抑制PDGF诱导的分支，而外源性FGF 7和-10完全恢复。总之，这些结果表明成纤维细胞生长因子在PDGF信号传导的下游起作用，PDGF信号传导调节神经嵴来源的间充质细胞和SMG分支形态发生中的Fgf表达。因此，PDGF信号传导是参与上皮和神经嵴源性间充质之间相互作用的可能机制。
A coordinated reciprocal interaction between epithelium and mesenchyme is involved in salivary gland morphogenesis. The submandibular glands (SMGs) of Wnt1-Cre/R26R mice have been shown positive for mesenchyme, whereas the epithelium is beta-galactosidase-negative, indicating that most mesenchymal cells are derived from cranial neural crest cells. Platelet-derived growth factor (PDGF) receptor alpha is one of the markers of neural crest-derived cells. In this study, we analyzed the roles of PDGFs and their receptors in the morphogenesis of mouse SMGs. PDGF-A was shown to be expressed in SMG epithelium, whereas PDGF-B, PDGFR alpha, and PDGFR beta were expressed in mesenchyme. Exogenous PDGF-AA and -BB in SMG organ cultures demonstrated increased levels of branching and epithelial proliferation, although their receptors were found to be expressed in mesenchyme. In contrast, short interfering RNA for Pdgfa and -b as well as neutralizing antibodies for PDGF-AB and -BB showed decreased branching. PDGF-AA induced the expression of the fibroblast growth factor genes Fgf3 and -7, and PDGF-BB induced the expression of Fgf1, -3, -7, and -10, whereas short interfering RNA for Pdgfa and Pdgfb inhibited the expression of Fgf3, -7, and -10, indicating that PDGFs regulate Fgf gene expression in SMG mesenchyme. The PDGF receptor inhibitor AG-17 inhibited PDGF-induced branching, whereas exogenous FGF7 and -10 fully recovered. Together, these results indicate that fibroblast growth factors function downstream of PDGF signaling, which regulates Fgf expression in neural crest-derived mesenchymal cells and SMG branching morphogenesis. Thus, PDGF signaling is a possible mechanism involved in the interaction between epithelial and neural crest-derived mesenchyme.