Estradiol regulates intestinal ABCG2 to promote urate excretion via the PI3K/Akt pathway.
Estradiol regulates intestinal ABCG2 to promote urate excretion via the PI3K/Akt pathway.
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雌二醇通过 PI3K/Akt 通路调节肠道 ABCG2 促进尿酸盐排泄
DOI：
10.1186/s12986-021-00583-y
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发表时间：
2021-06-18
影响因子：
4.5
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Liu L;Zhao T;Shan L;Cao L;Zhu X;Xue Y
目的研究高尿酸血症的性别差异，不仅可以为这一临床现象提供理论依据，而且可以为降尿酸治疗提供新的治疗靶点。本研究旨在证实雌二醇可通过PI 3 K/Akt途径促进肠ATP结合盒亚家族G成员2（ABCG 2）表达，从而增加尿酸排泄。采用高尿酸血症小鼠模型，观察雌二醇的降尿酸作用及肾脏和肠道ABCG 2表达的变化。建立了体内和体外肠道尿酸盐转运模型，以验证雌二醇对尿酸盐转运功能的调节作用。E2调节ABCG 2在肠细胞中表达的分子途径explored.ResultsThe雌二醇水平的高尿酸血症/痛风患者显着低于健康对照组。给雄性高尿酸血症小鼠和切除卵巢后的雌性小鼠施用苯甲酸雌二醇（EB）证实了雌二醇的降尿酸作用，高尿酸血症和雌二醇上调肠道ABCG 2的表达。在体内和体外的肠道尿酸排泄模型中，已经证实依匹林通过上调ABCG 2表达来促进尿酸盐转运。雌二醇通过PI 3 K/Akt通路调节肠道ABCG 2的表达，促进尿酸排泄，从而降低血清尿酸水平。
ObjectivesThe 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.MethodsThe 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.ResultsThe 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.ConclusionOur study revealed that estradiol regulates intestinal ABCG2 through the PI3K/Akt pathway to promote urate excretion, thereby reducing serum urate levels.
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影响因子：
4.6
作者：
Matsuo H;Ichida K;Takada T;Nakayama A;Nakashima H;Nakamura T;Kawamura Y;Takada Y;Yamamoto K;Inoue H;Oikawa Y;Naito M;Hishida A;Wakai K;Okada C;Shimizu S;Sakiyama M;Chiba T;Ogata H;Niwa K;Hosoyamada M;Mori A;Hamajima N;Suzuki H;Kanai Y;Sakurai Y;Hosoya T;Shimizu T;Shinomiya N
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16.6
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15.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Spiegel, Sarah
影响因子：
3.6
作者：
Merino, G;van Herwaarden, AE;Schinkel, AH
通讯作者：
Schinkel, AH