Wnt signaling in heart valve development and osteogenic gene induction.
Wnt signaling in heart valve development and osteogenic gene induction.
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DOI：
10.1016/j.ydbio.2009.11.030
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发表时间：
2010-02-15
影响因子：
2.7
通讯作者：
Yutzey, Katherine E.
中科院分区：
文献类型：
--
作者：
Alfieri, Christina M.;Cheek, Jonathan;Chakraborty, Santanu;Yutzey, Katherine E.
由β-连环蛋白介导的Wnt信号转导与早期内膜垫发育有关，但其在心脏瓣膜成熟和稳态后期的作用尚未确定。多种Wnt配体和途径基因在心脏瓣膜发育过程中差异表达。在E12.5，Wnt 2在垫间充质中表达，而Wnt 4和Wnt 9 b在覆盖的内皮细胞中占主导地位。在E17.5，Wnt 3a和Wnt 7 b在重构房室（AV）和半月瓣中表达。此外，TOPGAL Wnt报告基因在E16.5时在整个发育中的AV和半月瓣中具有活性，出生后在分层瓣叶中具有更多的局部表达。在鸡胚主动脉瓣中，成骨细胞谱系的特征性基因包括骨膜蛋白、骨连接蛋白和Id 2在E14时在富含胶原的纤维层中特异性表达。用成骨培养基处理培养的E14主动脉瓣间质细胞（维克）导致与骨形成相关的多种基因表达增加。用Wnt 3a处理维克IC导致β-连环蛋白的核定位和骨膜蛋白和基质gla-蛋白的诱导，但不诱导与骨生成后期相关的基因。总之，这些研究为Wnt信号传导作为内膜垫成熟以及瓣叶分层、稳态和发病机制的调节剂提供了证据。
Wnt signaling mediated by beta-catenin has been implicated in early endocardial cushion development, but its roles in later stages of heart valve maturation and homeostasis have not been identified. Multiple Wnt ligands and pathway genes are differentially expressed during heart valve development. At E12.5, Wnt2 is expressed in cushion mesenchyme, whereas Wnt4 and Wnt9b are predominant in overlying endothelial cells. At E17.5, both Wnt3a and Wnt7b are expressed in the remodeling atrioventricular (AV) and semilunar valves. In addition, the TOPGAL Wnt reporter transgene is active throughout the developing AV and semilunar valves at E16.5, with more localized expression in the stratified valve leaflets after birth. In chicken embryo aortic valves, genes characteristic of osteogenic cell lineages including periostin, osteonectin, and Id2 are expressed specifically in the collagen-rich fibrosa layer at E14. Treatment of E14 aortic valve interstitial cells (VIC) in culture with osteogenic media results in increased expression of multiple genes associated with bone formation. Treatment of VIC with Wnt3a leads to nuclear localization of beta-catenin and induction of periostin and matrix gla-protein, but does not induce genes associated with later stages of osteogenesis. Together, these studies provide evidence for Wnt signaling as a regulator of endocardial cushion maturation as well as valve leaflet stratification, homeostasis and pathogenesis.
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