Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development.

Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development.
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DOI:
10.1002/dvdy.21854
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发表时间:
2009-02
影响因子:
2.5
通讯作者:
Doetschman, Thomas
Doetschman, Thomas
中科院分区:
生物学3区
文献类型:
--
作者:
Azhar, Mohamad;Runyan, Raymond B.;Gard, Connie;Sanford, L. Philip;Miller, Marian L.;Andringa, Anastasia;Pawlowski, Sharon;Rajan, Sudarsan;Doetschman, Thomas

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转化生长因子β(TGFβ)在小鼠心脏垫上皮-间质转化(EMT)中的体内配体特异性知之甚少。为了阐明TGFβ在垫型EMT中的功能,我们使用体外和体内方法分析了胚胎第9.5天和E14.5天之间的Tgfb 1 −/−、Tgfb 2 −/−和Tgfb 3 −/−小鼠。E9.5时的房室(AV)管胶原凝胶试验表明Tgfb 1 −/−和Tgfb 3 −/−小鼠的EMT正常。然而,在E9.5和E10.5时对Tgfb 2 −/− AV外植体的分析表明,EMT(而不是垫细胞增殖)最初延迟,但后来保持持续。这与观察结果一致,即Tgfb 2 −/−胚胎,而不是Tgfb 1 −/−或Tgfb 3 −/−胚胎,在E14.5时发育扩大的缓冲区,EMT的有效指标水平升高。总的来说,这些数据表明,TGFβ2,而不是TGFβ1或TGFβ3,通过促进EMT的启动和终止来介导心脏垫EMT。
The ligand specificity of transforming growth factor beta (TGFβ) in vivo in mouse cardiac cushion epithelial-to-mesenchymal transition (EMT) is poorly understood. To elucidate the function of TGFβ in cushion EMT, we analyzed Tgfb1 −/−, Tgfb2−/− and Tgfb3−/− mice between embryonic day (E) 9.5 and E14.5 using both in vitro and in vivo approaches. Atrioventricular (AV) canal collagen gel assays at E9.5 indicated normal EMT in both Tgfb1−/− and Tgfb3−/− mice. However, analysis of Tgfb2−/− AV explants at E9.5 and E10.5 indicated that EMT, but not cushion cell proliferation, was initially delayed but later remained persistent. This was concordant with the observation that Tgfb2−/− embryos, and not Tgfb1−/− or Tgfb3−/− embryos, develop enlarged cushions at E14.5 with elevated levels of well validated indicators of EMT. Collectively, these data indicate that TGFβ2, and not TGFβ1 or TGFβ3, mediates cardiac cushion EMT by promoting both the initiation and cessation of EMT.
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