Potential involvement of Fgf10/Fgfr2 and androgen receptor (AR) in renal fibrosis in adult male rat offspring subjected to prenatal exposure to di-nbutyl phthalate (DBP)
Potential involvement of Fgf10/Fgfr2 and androgen receptor (AR) in renal fibrosis in adult male rat offspring subjected to prenatal exposure to di-nbutyl phthalate (DBP)
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DOI：
10.1016/j.toxlet.2017.09.009
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发表时间：
2018-01-05
影响因子：
3.5
通讯作者：
Jiang, Jun-Tao
中科院分区：
文献类型：
--
作者：
Sun, Wen-Lan;Zhu, Yi-Ping;Jiang, Jun-Tao
背景：我们先前证实，母亲接触邻苯二甲酸二丁酯(DBP)会导致新生儿男性子代肾脏发育不良和成人肾脏纤维化。但潜在的机制仍然难以捉摸。已知Fgf10/FGFR2和雄激素受体(AR)在肾脏发育中起重要作用。材料和方法：利用SD大鼠和大鼠肾近端小管细胞(NRK52E)，我们确定了Fgf10、FGFR2和AR在DBP诱导的肾纤维化中的潜在参与。这些动物血清睾酮浓度降低，Fgf10、FGFR2和AR表达减少。这是DBP作用下NRK52E细胞Fgf10、FGFR2和AR表达降低的趋势。此外，在异常肾组织和DBP处理的NRK52E细胞中，TGF-β和α-SMA的表达水平也较高。结论：Fgf10/FGFR2和AR可能参与了DBP致成年雄性大鼠子代肾脏纤维化的过程。DBP的抗雄激素作用可能在这一病理过程中起重要作用。
Background: We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) induces dysplasia of the kidney in newborn male offspring and renal fibrosis in adults. But the underlying mechanisms remain elusive. Fgf10/Fgfr2 and androgen receptor (AR) are known to be important for renal development. We therefore investigated whether these genes are involved in DBP-induced renal fibrosis.Materials and methods: Using Sprague-Dawley rats and rat renal proximal tubular cells (NRK52E), we determined the potential involvement of Fgf10, Fgfr2 and AR in DBP-induced renal fibrosis.Results: We found that maternal exposure to DBP induces renal fibrosis in adult male offspring. A lower serum testosterone concentration and reduced expression of Fgf10, Fgfr2 and AR were detected in these animals. These was a trend toward lower expression of Fgf10, Fgfr2 and AR in NRK52E cells subjected to DBP exposure. Furthermore, higher expression levels of TGF-beta and alpha-SMA were observed in abnormal renal tissue and DBP-treated NRK52E cells.Conclusion: Our findings suggest the potential involvement of Fgf10/Fgfr2 and AR in renal fibrosis of adult male rat offspring induced by prenatal exposure to DBP. The anti-androgenic effects of DBP might play an important role in this pathological process.