Soluble uric acid increases PDZK1 and ABCG2 expression in human intestinal cell lines via the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.
Soluble uric acid increases PDZK1 and ABCG2 expression in human intestinal cell lines via the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.
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可溶性尿酸通过 TLR4-NLRP3 炎性体和 PI3K/Akt 信号通路增加人肠细胞系中 PDZK1 和 ABCG2 的表达。
DOI：
10.1186/s13075-018-1512-4
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发表时间：
2018-02-07
影响因子：
4.9
通讯作者：
Wu H
中科院分区：
文献类型：
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作者：
Chen M;Lu X;Lu C;Shen N;Jiang Y;Chen M;Wu H
除了肾脏，肠道是参与尿酸排泄的最重要器官之一。然而，尿酸盐在肠道中排泄的机制仍不清楚。因此，探讨了可溶性尿酸与肠道排泄的关系。然后还检查了相关的信号分子。HT-29和Caco-2细胞系用可溶性尿酸刺激。蛋白质印迹和qRT-PCR用于测量蛋白质和mRNA水平。亚细胞分级分离方法和免疫荧光法用于定量不同亚细胞区室中的蛋白质。流式细胞术实验检测了ATP结合盒转运蛋白亚家族G成员2（ABCG 2）的功能。使用小干扰RNA转染来评估ABCG 2和含PDZ结构域1（PDZK 1）之间的相互作用。可溶性尿酸增加PDZK 1和ABCG 2的表达。可溶性尿酸的刺激也促进了ABCG 2从细胞内室到质膜的转运，并增加了其转运活性。此外，可溶性尿酸对PDZK 1和ABCG 2的上调被TLR 4-NLRP 3炎性小体抑制剂或PI 3 K/Akt信号传导抑制剂部分降低。此外，PDZK 1敲低显著抑制ABCG 2的表达和转运活性，而不管可溶性尿酸的激活，这表明PDZK 1在ABCG 2的调节中具有关键作用。这些结果表明，尿酸盐通过激活TLR 4-NLRP 3炎性体和PI 3 K/Akt信号通路上调PDZK 1和ABCG 2的表达，以便在肠细胞中排泄。本文的在线版本（10.1186/s13075-018-1512-4）包含补充材料，可供授权用户使用。
In addition to the kidney, the intestine is one of the most important organs involved in uric acid excretion. However, the mechanism of urate excretion in the intestine remains unclear. Therefore, the relationship between soluble uric acid and the gut excretion in human intestinal cells was explored. The relevant signaling molecules were then also examined. HT-29 and Caco-2 cell lines were stimulated with soluble uric acid. Western blotting and qRT-PCR were used to measure protein and mRNA levels. Subcellular fractionation methods and immunofluorescence were used to quantify the proteins in different subcellular compartments. Flow cytometry experiments examined the function of ATP-binding cassette transporter, subfamily G, member 2 (ABCG2). Small interfering RNA transfection was used to assess the interaction between ABCG2 and PDZ domain-containing 1 (PDZK1). Soluble uric acid increased the expression of PDZK1 and ABCG2. The stimulation of soluble uric acid also facilitated the translocation of ABCG2 from the intracellular compartment to the plasma membrane and increased its transport activity. Moreover, the upregulation of PDZK1 and ABCG2 by soluble uric acid was partially decreased by either TLR4-NLRP3 inflammasome inhibitors or PI3K/Akt signaling inhibitors. Furthermore, PDZK1 knockdown significantly inhibited the expression and transport activity of ABCG2 regardless of the activation by soluble uric acid, demonstrating a pivotal role for PDZK1 in the regulation of ABCG2. These findings suggest that urate upregulates the expression of PDZK1 and ABCG2 for excretion in intestinal cells via activating the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway. The online version of this article (10.1186/s13075-018-1512-4) contains supplementary material, which is available to authorized users.
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影响因子：
4.6
作者：
Matsuo H;Tsunoda T;Ooyama K;Sakiyama M;Sogo T;Takada T;Nakashima A;Nakayama A;Kawaguchi M;Higashino T;Wakai K;Ooyama H;Hokari R;Suzuki H;Ichida K;Inui A;Fujimori S;Shinomiya N
通讯作者：
Shinomiya N
影响因子：
3.3
作者：
Rho, Young Hee;Zhu, Yanyan;Choi, Hyon K.
通讯作者：
Choi, Hyon K.
影响因子：
4.6
作者：
Matsuo H;Nakayama A;Sakiyama M;Chiba T;Shimizu S;Kawamura Y;Nakashima H;Nakamura T;Takada Y;Oikawa Y;Takada T;Nakaoka H;Abe J;Inoue H;Wakai K;Kawai S;Guang Y;Nakagawa H;Ito T;Niwa K;Yamamoto K;Sakurai Y;Suzuki H;Hosoya T;Ichida K;Shimizu T;Shinomiya N
通讯作者：
Shinomiya N
影响因子：
4.9
作者：
Busso N;So A
通讯作者：
So A
影响因子：
16.6
作者：
通讯作者：
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