HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation.

HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation.
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DOI:
10.1016/j.ydbio.2003.09.019
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发表时间:
2004
影响因子:
2.7
通讯作者:
Yi Tan;Meiling Li;Sandra Cox;Marilyn K. Davis;O. Tawfik;B. Paria;S. Das
Yi Tan;Meiling Li;Sandra Cox;Marilyn K. Davis;O. Tawfik;B. Paria;S. Das
中科院分区:
生物学3区
文献类型:
--
作者:
Yi Tan;Meiling Li;Sandra Cox;Marilyn K. Davis;O. Tawfik;B. Paria;S. Das

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基质细胞多倍化是胚胎着床后子宫蜕膜化过程中的一种独特现象,其发生机制尚不清楚。一般认为,细胞周期中两个特定检查点G1至S和G2至M的细胞周期调控分子的异常表达和功能活性改变在细胞多倍性的发展中起重要作用。尽管内在细胞周期改变的令人信服的证据,它已经暗示,细胞多倍性的发展可能是由细胞外生长调节剂的具体行动控制。在这里,我们显示了一个新的作用肝素结合EGF样生长因子(HB-EGF)在小鼠基质细胞多倍体的发育过程中。HB-EGF是小鼠和人类中最早已知的植入分子介质之一,通过上调细胞周期蛋白D3促进基质细胞多倍体。腺病毒介导的反义细胞周期蛋白D3在体内外减弱细胞周期蛋白D3的表达并消除HB-EGF诱导的基质细胞多倍性。总的来说,这些结果表明,HB-EGF诱导的基质细胞多倍体和蜕膜化的调节依赖于细胞周期蛋白D3的诱导。
Stromal cell polyploidy is a unique phenomenon that occurs during uterine decidualization following embryo implantation, although the developmental mechanism still remains elusive. The general consensus is that the aberrant expression and altered functional activity of cell cycle regulatory molecules at two particular checkpoints G1 to S and G2 to M in the cell cycle play an important role in the development of cellular polyploidy. Despite the compelling evidence of intrinsic cell cycle alteration, it has been implicated that the development of cellular polyploidy may be controlled by specific actions of extracellular growth regulators. Here we show a novel role for heparin-binding EGF-like growth factor (HB-EGF) in the developmental process of stromal cell polyploidy in mice. HB-EGF, which is one of the earliest known molecular mediators of implantation in mice and humans, promotes stromal cell polyploidy via upregulation of cyclin D3. Adenoviral delivery of antisense cyclin D3 attenuates cyclin D3 expression and abrogates HB-EGF-induced stromal cell polyploidy in vitro and in vivo. Collectively, the results demonstrate that the regulation of stromal cell polyploidy and decidualization induced by HB-EGF depend on cyclin D3 induction.