An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus.

An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus.
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DOI:
10.1080/17425255.2018.1499726
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发表时间:
2018-08
影响因子:
4.3
通讯作者:
Mao Q
Mao Q
中科院分区:
医学2区
文献类型:
--
作者:
Han LW;Gao C;Mao Q

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P-gp/ABCB1 和 BCRP/ABCG2 在整个妊娠期的胎盘和胎儿中高度表达,可以在生长发育的敏感时期调节脆弱胎儿的药物和外源性物质的暴露和毒性。我们的目的是提供关于不同物种中两种转运蛋白的胎盘和胎儿表达的最新知识,并提供关于解释转运蛋白表达和胎儿暴露相对于药物转运分数概念的见解。通过 PubMed(主要是 2010 年 7 月至 2018 年 2 月)对 P-gp 和 BCRP 在主要人类、小鼠、大鼠和豚鼠胎盘和胎儿中的表达和功能进行综合文献综述。虽然不同物种的胎盘和胎儿组织中 P-gp 和 BCRP 的表达和功能有许多共性,但表达水平和时间变化存在明显差异。需要进一步的研究来量化这些转运蛋白的蛋白质丰度,并在功能上评估它们在不同妊娠阶段的活性。结合物种间差异的知识和药物转运分数的概念,我们可以更好地预测这些转运蛋白对胎儿药物暴露的影响程度。
P-gp/ABCB1 and BCRP/ABCG2 are highly expressed in the placenta and fetus throughout gestation and can modulate exposure and toxicity of drugs and xenobiotics to the vulnerable fetus during the sensitive times of growth and development. We aim to provide an update on current knowledge on placental and fetal expressions of the two transporters in different species, and to provide insight on interpreting transporter expression and fetal exposure relative to the concept of fraction of drug transported. Comprehensive literature review through PubMed (primarily from July 2010 to February 2018) on P-gp and BCRP expression and function in the placenta and fetus of primarily human, mouse, rat, and guinea pig. While there are many commonalities in the expression and function of P-gp and BCRP in the placenta and fetal tissues across species, there are distinct differences in expression levels and temporal changes. Further studies are needed to quantify protein abundance of these transporters and functionally assess their activities at various gestational stages. Combining the knowledge of interspecies differences and the concept of fraction of drug transported, we may better predict the magnitude of impact these transporters have on fetal drug exposure.
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