Estradiol Regulates Intestinal ABCG2 to Promote Urate Excretion Via the PI3K/Akt Pathway

Overview

Journal Nutr Metab (Lond)

Publisher Biomed Central

Date 2021 Jun 19

PMID 34144706

Citations 13

Authors

Lei Liu

Tianyi Zhao

Lizhen Shan

Ling Cao

Xiaoxia Zhu

Yu Xue

Affiliations

Soon will be listed here.

Abstract

Objectives: The study of sex differences in hyperuricemia can provide not only a theoretical basis for this clinical phenomenon but also new therapeutic targets for urate-lowering therapy. In the current study, we aimed to confirm that estradiol can promote intestinal ATP binding cassette subfamily G member 2 (ABCG2) expression to increase urate excretion through the PI3K/Akt pathway.

Methods: The estradiol levels of hyperuricemia/gout patients and healthy controls were compared, and a hyperuricemia mouse model was used to observe the urate-lowering effect of estradiol and the changes in ABCG2 expression in the kidney and intestine. In vivo and in vitro intestinal urate transport models were established to verify the urate transport function regulated by estradiol. The molecular pathway by which estradiol regulates ABCG2 expression in intestinal cells was explored.

Results: The estradiol level of hyperuricemia/gout patients was significantly lower than that of healthy controls. Administering estradiol benzoate (EB) to both male hyperuricemic mice and female mice after removing the ovaries confirmed the urate-lowering effect of estradiol, and hyperuricemia and estradiol upregulated the expression of intestinal ABCG2. Estradiol has been confirmed to promote urate transport by upregulating ABCG2 expression in intestinal urate excretion models in vivo and in vitro. Estradiol regulates the expression of intestinal ABCG2 through the PI3K/Akt pathway.

Conclusion: Our study revealed that estradiol regulates intestinal ABCG2 through the PI3K/Akt pathway to promote urate excretion, thereby reducing serum urate levels.

Citing Articles

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