The xenobiotic transporter ABCG2 plays a novel role in differentiation of trophoblast-like BeWo cells

The xenobiotic transporter ABCG2 plays a novel role in differentiation of trophoblast-like BeWo cells
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DOI:
10.1016/j.placenta.2006.12.003
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发表时间:
2007-04-01
期刊:
影响因子:
3.8
通讯作者:
Keelan, J. A.
Keelan, J. A.
中科院分区:
医学3区
文献类型:
--
作者:
Evseenko, D. A.;Paxton, J. W.;Keelan, J. A.

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滋养层细胞在细胞融合过程中经历质膜脂质不对称性的丧失,而没有进一步进展到凋亡的终末阶段。在此过程中提供细胞存活的抗凋亡机制的性质是未知的。使用BeWo细胞模型,我们探讨了异生物质/脂质转运蛋白ABCG 2在促进毛喉素诱导分化过程中的细胞存活中的作用。通过siRNA抑制ABCG 2表达导致磷脂酰丝氨酸外化显著增加,随后是神经酰胺的积累和细胞凋亡增加。ABCG 2沉默降低了合胞体形成标志物(β-hCG和HERV-W)的表达,但融合不受影响。这些研究结果表明,ABCG 2保护细胞在短暂的膜不稳定与细胞分化和融合,突出了一个新的,以前未认识到的作用,ABCG 2作为一个生存因子在胎盘合胞体的形成。(c)2007年由IFPA和Elsevier Ltd.出版
Trophoblast cells undergo loss of plasma membrane lipid asymmetry during cell fusion without further progression to terminal phases of apoptosis. The nature of the anti-apoptotic mechanisms providing cell survival during this process is unknown. Using a BeWo cell model, we explored the role of the xenobiotic/lipid transporter ABCG2 in promoting cell survival during forskolin-induced differentiation. Suppression of ABCG2 expression by siRNA led to a marked increase in phosphatidylserine externalisation followed by accumulation of ceramides and increased apoptosis. Expression of markers of syncytial formation (beta-hCG and HERV-W) was decreased by ABCG2 silencing, although fusion was unaffected. These findings suggest that ABCG2 protects cells during the period of transient membrane instability associated with cell differentiation and fusion, highlighting a novel, previously unrecognised role of ABCG2 as a survival factor during the formation of the placental syncytium. (c) 2007 Published by IFPA and Elsevier Ltd.