Regulation of the placental BCRP transporter by PPAR gamma.
Regulation of the placental BCRP transporter by PPAR gamma.
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DOI：
10.1002/jbt.21880
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发表时间：
2017-05
影响因子：
3.6
通讯作者：
Aleksunes LM
中科院分区：
文献类型：
--
作者：
Lin Y;Bircsak KM;Gorczyca L;Wen X;Aleksunes LM
识别胎盘乳腺癌耐药蛋白 (BCRP) 表达的调节因子至关重要，因为该转运蛋白的下调可能会增加胎儿对异生素的暴露。在这里，我们试图测试核受体过氧化物酶体增殖物激活受体 γ (PPARγ) 是否调节胎盘中 BCRP 的表达。为了测试这一点，将人 BeWo 胎盘绒毛膜癌细胞与 PPARγ 激动剂罗格列酮或 PPARγ 拮抗剂 T0070907 一起培养 24 小时。 PPARγ 激动剂治疗后，合胞化标记物 GCM1 和 hCGβ 以及 BCRP 的信使 RNA (mRNA) 表达增加。相反，PPARγ 拮抗剂治疗后 BCRP mRNA 和蛋白表达下降 30-50%。罗格列酮增强 BCRP 蛋白表达和转运活性，导致底物 Hoechst 33342 的流出量比对照细胞增加 20%。这些结果表明 PPARγ 可以上调胎盘中 BCRP 的表达，这对于理解保护胎儿在发育过程中免受异生素暴露的机制可能很重要。
Identifying regulators of placental breast cancer resistance protein (BCRP) expression is critical as down-regulation of this transporter may increase exposure of the fetus to xenobiotics. Here we sought to test whether the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) regulates BCRP expression in the placenta. To test this, human BeWo placental choriocarcinoma cells were cultured with the PPARγ agonist rosiglitazone or the PPARγ antagonist T0070907 for 24 h. Messenger RNA (mRNA) expression of syncytialization markers, GCM1 and hCGβ, as well as BCRP increased with PPARγ agonist treatment. Conversely, BCRP mRNA and protein expression decreased 30–50% with PPARγ antagonist treatment. Rosiglitazone enhanced BCRP protein expression and transport activity, resulting in a 20% greater efflux of the substrate Hoechst 33342 compared to control cells. These results suggest that PPARγ can up-regulate BCRP expression in the placenta, which may be important in understanding mechanisms that protect the fetus from xenobiotic exposure during development.