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首页> 外文OA文献 >Meta-analysis of Expression of Hepatic Organic Anion Transporting Polypeptide (OATP) Transporters in Cellular Systems Relative to Human Liver Tissue
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Meta-analysis of Expression of Hepatic Organic Anion Transporting Polypeptide (OATP) Transporters in Cellular Systems Relative to Human Liver Tissue

机译：肝细胞系统中肝脏有机阴离子转运多肽（OaTp）转运蛋白表达的meta分析

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摘要

Organic anion transporting polypeptide (OATP)1B1, OATP1B3 and OATP2B1 transporters play an important role in hepatic drug disposition. Recently, an increasing number of studies have reported proteomic expression data for OATP transporters. However, systematic analysis and understanding of the actual differences in OATP expression between liver tissue and commonly used cellular systems is lacking. In the current study, meta-analysis was performed to assess the protein expression of OATP transporters reported in hepatocytes relative to liver tissue and identify any potential correlations in transporter expression levels in the same individual. OATP1B1 was identified as the most abundant uptake transporter at 5.9 ± 8.3, 5.8 ± 3.3 and 4.2 ± 1.7 fmol/μg protein in liver tissue, sandwich-cultured human hepatocytes (SCHH) and cryopreserved suspended hepatocytes, respectively. The rank order in average expression in liver tissue and cellular systems was OATP1B1 OATP1B3 ≈ OATP2B1. Abundance levels of the OATP transporters investigated were not significantly different between liver and cellular systems, with the exception of OATP2B1 expression in SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3 and OATP2B1 liver expression data in the same individuals (n = 86) identified weak (OATP1B1/OATP2B1) to moderate (OATP1B3/OATP2B1) significant correlations. A significant weak correlation was noted between OATP1B1 abundance and age of human donors, whereas expression of the OATPs investigated was independent of sex. Implications of the current analysis on the in vitro-in vivo extrapolation of transporter-mediated drug disposition using physiologically-based pharmacokinetic models are discussed.
机译：有机阴离子转运多肽（OATP）1B1，OATP1B3和OATP2B1转运蛋白在肝药物处置中起重要作用。最近，越来越多的研究报告了OATP转运蛋白的蛋白质组表达数据。但是，缺乏对肝组织和常用细胞系统之间OATP表达实际差异的系统分析和了解。在当前的研究中，进行了荟萃分析，以评估肝细胞中相对于肝组织报道的OATP转运蛋白的蛋白表达，并确定同一个人中转运蛋白表达水平的任何潜在相关性。 OATP1B1被认为是肝组织，夹心培养的人肝细胞（SCHH）和冷冻保存的悬浮肝细胞中最丰富的摄取转运蛋白，分别为5.9±8.3、5.8±3.3和4.2±1.7 fmol /μg蛋白。在肝组织和细胞系统中平均表达的排名顺序是OATP1B1> OATP1B3≈OATP2B1。在肝和细胞系统之间，所研究的OATP转运蛋白的丰度水平没有显着差异，除了SCHH中相对于肝组织的OATP2B1表达。分析同一个人（n = 86）中OATP1B1，OATP1B3和OATP2B1肝表达数据后，发现弱（OATP1B1 / OATP2B1）与中度（OATP1B3 / OATP2B1）显着相关。 OATP1B1的丰度与人类供体的年龄之间存在显着的弱相关性，而所研究的OATP的表达与性别无关。讨论了当前分析对基于生理学的药代动力学模型的转运蛋白介导的药物处置的体外-体内外推的含义。

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