Taniguchi Tatsuya, Zanetti-Yabur Alana, Wang Pijun, Usyk Mykhaylo, Burk Robert D, Wolkoff Allan W
Marion Bessin Liver Research Center Albert Einstein College of Medicine and Montefiore Medical Center Bronx NY.
Division of Hepatology Albert Einstein College of Medicine and Montefiore Medical Center Bronx NY.
Hepatol Commun. 2020 Mar 11;4(5):739-752. doi: 10.1002/hep4.1489. eCollection 2020 May.
The liver plays an essential role in removing endogenous and exogenous compounds from the circulation. This function is mediated by specific transporters, including members of the family of organic anion transport proteins (OATPs) and the Na-taurocholate transporting polypeptide (NTCP). In the present study, transporter protein expression was determined in liver samples from patients with cirrhosis or controls without liver disease. Five transporters (OATP1A2, OATP1B1, OATP1B3, OATP2B1, and NTCP) were studied. Transporter content in homogenates of human liver was quantified on western blots probed with transporter-specific antibodies in which a calibrated green fluorescent protein-tagged transporter standard was included. Liver samples from 21 patients with cirrhosis (hepatitis C in 17 and alcohol abuse in 4) and 17 controls without liver disease were analyzed. Expression of each of the transporters had a large spread, varying by an order of magnitude in cirrhotic and control livers. OATP1B1 was the most abundant transporter in controls ( < 0.01) but was significantly lower in cirrhotic livers as was NTCP expression ( < 0.01). There was little difference in transporter expression with respect to age or sex. Despite the large variability in transporter expression within a group, analysis in individuals showed that those with high or low expression of one transporter had a similar magnitude in expression of the others. Differences in transporter expression could explain unanticipated heterogeneity of drug transport and metabolism in individuals with and without liver disease.
肝脏在清除循环中的内源性和外源性化合物方面发挥着重要作用。这一功能由特定的转运蛋白介导，包括有机阴离子转运蛋白（OATP）家族成员和牛磺胆酸钠转运多肽（NTCP）。在本研究中，测定了肝硬化患者或无肝病对照者肝脏样本中的转运蛋白表达。研究了五种转运蛋白（OATP1A2、OATP1B1、OATP1B3、OATP2B1和NTCP）。用人肝脏匀浆中的转运蛋白含量在western印迹上进行定量，印迹上用转运蛋白特异性抗体进行检测，并包含校准的绿色荧光蛋白标记的转运蛋白标准品。分析了21例肝硬化患者（17例丙型肝炎患者和4例酒精滥用患者）和17例无肝病对照者的肝脏样本。每种转运蛋白的表达差异很大，在肝硬化和对照肝脏中相差一个数量级。OATP1B1是对照中最丰富的转运蛋白（<0.01），但在肝硬化肝脏中显著降低，NTCP表达也是如此（<0.01）。转运蛋白表达在年龄或性别方面差异不大。尽管组内转运蛋白表达存在很大变异性，但个体分析表明，一种转运蛋白高表达或低表达的个体，其他转运蛋白的表达量也相似。转运蛋白表达的差异可以解释有肝病和无肝病个体中药物转运和代谢意外的异质性。
