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Toxicol Lett. 2018 Jan 5;282:37-42. doi: 10.1016/j.toxlet.2017.09.009. Epub 2017 Sep 15.

Potential involvement of Fgf10/Fgfr2 and androgen receptor (AR) in renal fibrosis in adult male rat offspring subjected to prenatal exposure to di-n-butyl phthalate (DBP).

Author information

1
Department of Geriatrics, Shanghai General Hospital of Nanjing Medical University,100 Haining Road, Shanghai 200080, China.
2
Department of Urology, Shanghai General Hospital of Nanjing Medical University,100 Haining Road, Shanghai 200080, China.
3
Department of Geriatrics, the First Hospital Affiliated to Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China. Electronic address: dinggx@njmu.edu.cn.
4
Department of Urology, Shanghai General Hospital of Nanjing Medical University,100 Haining Road, Shanghai 200080, China. Electronic address: tianyi_xyz@163.com.

Abstract

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-β and α-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.

KEYWORDS:

Androgen receptor; Di-n-butyl phthalate; Fibroblast growth factor 10; Fibroblast growth factor receptor 2; Renal fibrosis

PMID:
28919491
DOI:
10.1016/j.toxlet.2017.09.009
[Indexed for MEDLINE]

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