Activation of the RhoA/ROCK pathway contributes to renal fibrosis in offspring rats induced by maternal exposure to di-n-butyl phthalate.

ABSTRACT

Maternal exposure to di-n-butyl phthalate (DBP) can cause renal fibrosis in adult offspring rats. However, its underlying mechanisms have not yet been fully understood. In this study, we investigated whether the RhoA/ROCK pathway plays an important role in offspring renal fibrosis induced by maternal exposure to DBP. Our results showed that maternal exposure to DBP (850 mg/kg/day orally feeding during gestational days 14-18) activated the RhoA/ROCK pathway and induced epithelial-mesenchymal transition (EMT) in kidneys of offspring rats. Compared with the control group treated with normal saline, EMT in the kidneys of offspring rats undergoing 8 weeks of ROCK inhibitor Y-27632 treatment (at a dose of 30 mg/kg) was significantly inhibited, the degree of renal fibrosis was significantly reduced, and the renal function was significantly improved. DBP (10 µmol/L) activated the RhoA/ROCK pathway and induced EMT in NRK-52E cells in vitro. Both 5 µM and 10 µM Y-27632, a ROCK inhibitor, significantly reduced the EMT of NRK-52E cells. Taken together, our findings suggest that the RhoA/ROCK pathway plays an important role in the pathogenesis of renal fibrosis in offspring rats induced by maternal exposure to DBP via promoting EMT of renal tubular epithelial cells.