TGF-β induces Smad2 Phosphorylation, ARE Induction, and Trophoblast Differentiation.
TGF-β induces Smad2 Phosphorylation, ARE Induction, and Trophoblast Differentiation.
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DOI：
10.15283/ijsc17069
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发表时间：
2018-05-30
影响因子：
2.3
通讯作者：
Brown TL
中科院分区：
文献类型：
--
作者：
Albers RE;Selesniemi K;Natale DRC;Brown TL
转化生长因子β (TGF-β)信号传导已被证明可以控制大量关键的细胞活动，如细胞死亡、分化和发育，并被认为是胎盘功能的主要调节因子。SM10细胞是一种小鼠胎盘祖细胞系，经TGF-β处理后可分化为转运营养物质的迷路样细胞。然而，TGF-β激活诱导SM10祖细胞分化的信号转导通路尚未得到充分研究。本研究以SM10迷路祖细胞系为研究对象，探讨TGF-β对迷路祖细胞的诱导分化作用。通过光镜、荧光素酶测定和Western blot分析研究TGF-β通路的激活和TGF-β诱导分化的能力。在本报告中，我们发现TGF-β的三种亚型具有最终分化SM10细胞的能力，而TGF-β超家族的其他主要成员，Nodal和Activin A则没有。此外，我们已经确定TGF-β诱导的Smad2磷酸化可以通过ALK-5受体介导，随后激活激活素反应元件。我们的研究确定了SM10祖细胞中参与迷路滋养细胞分化的重要调控信号通路。
Transforming growth factor beta (TGF-β) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-β. However, the signal transduction pathway activated by TGF-β to induce SM10 progenitor differentiation has yet to be fully investigated. In this study the SM10 labyrinthine progenitor cell line was used to investigate TGF-β induced differentiation. Activation of the TGF-β pathway and the ability of TGF-β to induce differentiation were investigated by light microscopy, luciferase assays, and Western blot analysis. In this report, we show that three isoforms of TGF-β have the ability to terminally differentiate SM10 cells, whereas other predominant members of the TGF-β superfamily, Nodal and Activin A, do not. Additionally, we have determined that TGF-β induced Smad2 phosphorylation can be mediated via the ALK-5 receptor with subsequent transactivation of the Activin response element. Our studies identify an important regulatory signaling pathway in SM10 progenitor cells that is involved in labyrinthine trophoblast differentiation.