TY - JOUR
T1 - Interindividual Diversity in Expression of Organic Anion Uptake Transporters in Normal and Cirrhotic Human Liver
AU - Taniguchi, Tatsuya
AU - Zanetti-Yabur, Alana
AU - Wang, Pijun
AU - Usyk, Mykhaylo
AU - Burk, Robert D.
AU - Wolkoff, Allan W.
N1 - Publisher Copyright:
© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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 (P < 0.01) but was significantly lower in cirrhotic livers as was NTCP expression (P < 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. Conclusion: Differences in transporter expression could explain unanticipated heterogeneity of drug transport and metabolism in individuals with and without liver disease.
AB - 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 (P < 0.01) but was significantly lower in cirrhotic livers as was NTCP expression (P < 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. Conclusion: Differences in transporter expression could explain unanticipated heterogeneity of drug transport and metabolism in individuals with and without liver disease.
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U2 - 10.1002/hep4.1489
DO - 10.1002/hep4.1489
M3 - Article
AN - SCOPUS:85099865923
SN - 2471-254X
VL - 4
SP - 739
EP - 752
JO - Hepatology Communications
JF - Hepatology Communications
IS - 5
ER -