17beta-estradiol Attenuates Renal Fibrosis in Mice with Obstructive Uropathy

ABSTRACT

PURPOSE: Men are generally more prone to chronic renal disease and progression to end stage renal disease than women. The purpose of this study is to prove the effect of gender and sex hormone on renal fibrosis in mice with unilateral ureteral obstruction (UUO) and to elucidate the specific underlying mechanisms. METHODS: We compared the expression of alpha-smooth muscle actin (alpha-SMA) in female and male mice with complete UUO (day 7). After this, we estimated the changes of renal fibrosis in the female mice with oophorectomy and in the female mice with oophorectomy and replacement of 17beta-estradiol, respectively. RESULTS: The level of alpha-SMA in the female kidney with UUO was significantly lower than that in the male kidney with UUO. oophorectomy and replacement of 17beta-estradiol did not change the expression of angiotensin II type 1 (AT1) receptor in the female kidney with UUO, whereas the expression of angiotensin II type 2 (AT2) receptor was significantly more elevated in the intact female (IF) and the oophorectomized female with estrogen (OF+E) than that in the oophorectomized female (OF). The expressions of inducible nitric oxide synthase (iNOS) in the IF and OF+E mice were significantly more elevated than that in the OF mice, which was similar to the expression of AT2 receptor. CONCLUSION: The female gender is associated with resistance to renal fibrosis in obstructive uropathy and this gender difference may originate from the existence of 17beta-estradiol, which has an anti-fibrotic effect via upregulation of the AT2 receptor and iNOS.