Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis.
Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis.
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溶质载体有机阴离子转运蛋白家族成员 3A1 是胆汁酸流出转运蛋白在胆汁淤积中的作用
DOI：
10.1053/j.gastro.2018.07.031
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发表时间：
2018-11
期刊：
影响因子：
29.4
通讯作者：
Chai J
中科院分区：
文献类型：
--
作者：
Pan Q;Zhang X;Zhang L;Cheng Y;Zhao N;Li F;Zhou X;Chen S;Li J;Xu S;Huang D;Chen Y;Li L;Wang H;Chen W;Cai SY;Boyer JL;Chai J
胆汁转运蛋白维持胆汁酸的稳态。
我们使用实时数量的PCR，免疫印迹和免疫荧光分析进行了实验，我们测量了22例胆汁淤积患者的Oatp3A1蛋白和mRNA的水平，并在22例没有胆汁淤积的患者的肝脏组织中定位蛋白质。 IGATION（BDL）或假手术在1％的饮食中诱导胆汁淤积或对照饮食，并分析了肝酸的水平；
Oatp3A1 mRNA和蛋白质的肝含量显着增加，来自胆汁淤积的患者和ca饮食诱导的1％Ca饮食诱导的成纤维细胞生长因子19（FGF19，FGF15）的啮齿动物（FGF15）在肝脏中的核心sps 1也增加了。 -kappa b （NF-κB）在肝细胞中增加OATP3A1的表达； Yroxine进入细胞和外排胆酸。
我们发现，与健康的肝组织相比，患者和啮齿动物的胆固性肝组织中的OATP3A1水平升高。
Background & AimsBile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis.MethodsWe measured levels of OATP3A1 protein and messenger RNA and localized the protein in liver tissues from 22 patients with cholestasis and 21 patients without cholestasis, using real-time quantitative polymerase chain reaction, immunoblot, and immunofluorescence analyses. We performed experiments withSlco3a1-knockout and C57BL/6J (control) mice. Mice and Sprague-Dawley rats underwent bile duct ligation (BDL) or a sham operation. Some mice were placed on a 1% cholic acid (CA) diet to induce cholestasis or on a control diet. Serum and liver tissues were collected and analyzed; hepatic levels of bile acids and 7-α-C4 were measured using liquid chromatography/mass spectrometry. Human primary hepatocytes and hepatoma (PLC/PRF/5) cell lines were used to study mechanisms that regulate OATP3A1 expression and transport.ResultsHepatic levels of OATP3A1 messenger RNA and protein were significantly increased in liver tissues from patients with cholestasis and from rodents with BDL or 1% CA diet–induced cholestasis. Levels of fibroblast growth factor 19 (FGF19, FGF15 in rodents) were also increased in liver tissues from patients and rodents with cholestasis. FGF19 signaling activated the Sp1 transcription factor and nuclear factor κB to increase expression of OATP3A1 in hepatocytes; we found binding sites for these factors in theSLCO3A1promoter.Slco3a1-knockout mice had shorter survival times and increased hepatic levels of bile acid, and they developed more liver injury after the 1% CA diet or BDL than control mice. In hepatoma cell lines, we found OATP3A1 to take prostaglandin E2 and thyroxine into cells and efflux bile acids.ConclusionsWe found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.
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影响因子：
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作者：
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影响因子：
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