Maternal exposure to di-n-butyl phthalate promotes Snail1-mediated epithelial-mesenchymal transition of renal tubular epithelial cells via upregulation of TGF-beta1 during renal fibrosis in rat offspring.
Maternal exposure to di-n-butyl phthalate promotes Snail1-mediated epithelial-mesenchymal transition of renal tubular epithelial cells via upregulation of TGF-beta1 during renal fibrosis in rat offspring.
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母体暴露于邻苯二甲酸二正丁酯可在大鼠后代肾纤维化过程中通过上调 TGF-β1 促进 Snail1 介导的肾小管上皮细胞上皮间质转化。
DOI：
10.1016/j.ecoenv.2018.10.073
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发表时间：
2019
影响因子：
6.8
通讯作者：
Han Bang-Min
中科院分区：
文献类型：
--
作者：
Zhao Sheng;Jiang Jun-Tao;Li Deng;Zhu Yi-Ping;Xia Shu-Jie;Han Bang-Min
我们以前证明，母体暴露于邻苯二甲酸二丁酯（DBP）导致雄性后代的肾纤维化;然而，迄今为止，这种影响的潜在机制尚未得到彻底阐明。我们假设DBP暴露诱导纤维化肾脏中TGF-β表达和上皮-间质转化（EMT）的异常激活。妊娠大鼠在妊娠第14-18天经口给予DBP，剂量为850 mg/kg BW/天。免疫组织化学染色显示DBP暴露组TGF-β1和EMT标志物表达增加。在大鼠肾小管上皮细胞（NRK 52 E）中，ROS的产生增加了TGF-β1的表达水平，随后促进了Snail 1介导的EMT的诱导。值得注意的是，DBP暴露也促进了下调TGF-β1的自噬。总之，我们的研究结果表明，母体暴露于DBP通过上调TGF-β1促进肾小管上皮细胞的EMT。
We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) resulted in renal fibrosis in male offspring; however, the underlying mechanism governing this effect has not been thoroughly elucidated to date. We hypothesized that DBP exposure induces TGF-β expression and abnormal activation of epithelial-mesenchymal transition (EMT) in fibrotic kidneys. Pregnant rats received DBP orally at a dose of 850 mg/kg BW/day during gestational days 14–18. In the DBP-exposed group, immunohistochemistry (IHC) staining showed increased expression of TGF-β1 and EMT markers. In rat kidney tubular epithelial cells (NRK52E), ROS production increased expression levels of TGF-β1 and subsequently contributed to the induction of Snail1-mediated EMT. Notably, DBP exposure also promoted autophagy that downregulated TGF-β1. Taken together, our findings suggest that maternal exposure to DBP promotes EMT in tubular epithelial cells via upregulation of TGF-β1.