The effect of estradiol on renal tubular exression of ATP-binding cassette superfamily member 2 via PI3K/Akt pathway / 中华风湿病学杂志

ABSTRACT

Objective To compare the serum estradiol level of gouty patients with healthy controls and to investigate whether estradiol upregulatesthe expression of the uric acid transporter ATP-binding cassette superfamily member 2 (ABCG2) of human renal tubular epithelial cells (HK-2)..Methods Serum of 16 male gout patients and 16 male healthy controls and their estradiol level were assessed with ELISA.The HK-2 cells wer cultured with different concentrations of estradiol for 24 hours or 48 hours.mRNA expression of ABCG2 was assessed by quantitative polymerase chain reaction (qPCR).HK-2 cells were cultured with estradiol or estradiol and inhibitor of PI3K/Akt pathway LY294002.mRNA expression of ABCG2 was assessed by qPCR,while the Akt,p-Ser473-Akt,p-Thr308-Akt and ABCG2 expression were investigated by Western blot.Data was analyzed using either the one-way analysis of variance or the t test.Results The level of serum uric acid in gout patients was [(547±18) μmol/L],which was significantly higher than that of healthy controls [(344±12) μmol/L),t=-5.395,P＜0.01].The level of estradiol in gout patients was (45±6) μmol/L,which was significantly lower than that of healthy controls [(100±8) μmol/L,t=9.375,P＜0.01].The mRNA expression of ABCG2 of 10-4 mol/L estradiol group was elevated after 24 hours or 48 hours (t=3.168,t=3.990;P＜0.01).In the group of co-stimulation withestradiol and LY294002,the ABCG2,p-Ser473-Akt and p-Thr308-Akt expression were down regulated compared to the estradiol group.Conclusion There is a significant correlation between serum estradiol and uric acid.Estradiol inducesthe expression of ABCG2 of HK-2 cells by activating PI3K/Akt pathway.