Hepatitis C Virus-related Cirrhosis is a Major Determinant of the Expression Levels of Hepatic Drug Transporters
Hepatitis C Virus-related Cirrhosis is a Major Determinant of the Expression Levels of Hepatic Drug Transporters
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DOI：
10.2133/dmpk.25.190
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发表时间：
2010-01-01
影响因子：
2.1
通讯作者：
Inui, Ken-ichi
中科院分区：
文献类型：
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作者：
Ogasawara, Ken;Terada, Tomohiro;Inui, Ken-ichi
肝脏药物转运蛋白负责药物的肝脏摄取和胆汁排泄在各种病理生理条件下已经观察到肝脏药物转运蛋白基因的表达变化但是，尚未全面研究哪些因素显着影响肝脏药物转运蛋白的mRNA水平在本研究中，我们使用非癌性肝组织样本定量了17种药物转运蛋白的mRNA表达，并进行逐步多元回归分析，从18个临床变量中识别影响其表达的因素17种药物转运蛋白中，有机阴离子转运多肽（OATP）2B1的mRNA水平最高。其次是有机阳离子转运蛋白1。有机阴离子转运蛋白2，OATP1B1。 OATP1B3、多药耐药相关蛋白 (MRP) 6 和 MRP3 逐步多元回归分析表明，在 17 种药物转运蛋白中，预测 MRP4 mRNA 水平的准确度最高 在进入 MRP4 预测模型的临床变量中，丙型肝炎病毒 (HCV) 感染和肝硬化是影响 MRP4 mRNA 和蛋白水平的关键因素 此外，HCV 相关肝硬化还影响除 MRP4 之外的 8 种药物转运蛋白的 mRNA 水平 这些结果表明认为HCV相关性肝硬化是影响肝脏药物转运蛋白表达的关键因素。特别是MRP4
Hepatic drug transporters are responsible for both hepatic uptake and the biliary excretion of drugs Expression changes in hepatic drug transporter genes have been observed in various pathophysiological conditions However, it has not been comprehensively investigated what factors substantially influence the mRNA levels of hepatic drug transporters In this study, we quantified the mRNA expression of 17 drug transporters using noncancerous liver tissue samples and carried out stepwise multiple regression analysis to identify the factors affecting their expression from 18 clinical variables For 17 drug transporters, the mRNA level of organic anion transporting polypeptide (OATP) 2B1 was highest. followed by that of organic cation transporter 1. organic anion transporter 2, OATP1B1. OATP1B3, multidrug resistance-associated protein (MRP) 6, and MRP3 Stepwise multiple regression analysis demonstrated MRP4 mRNA level to be predicted with the greatest accuracy among 17 drug transporters Of clinical variables entered into the prediction model for MRP4, hepatitis C virus (HCV) infection and liver cirrhosis were crucial factors affecting MRP4 mRNA and protein levels Furthermore, HCV-related cirrhosis influenced the mRNA levels of 8 drug transporters besides MRP4 These findings indicate that HCV-related cirrhosis is a crucial factor affecting the expression of hepatic drug transporters. especially MRP4