Court Michael H, Zhang Xiuling, Ding Xinxin, Yee Karen K, Hesse Leah M, Finel Moshe
Department of Molecular Physiology and Pharmacology, Comparative and Molecular Pharmacogenomics Laboratory, Tufts University School of Medicine, Boston, MA, USA.
Xenobiotica. 2012 Mar;42(3):266-77. doi: 10.3109/00498254.2011.618954. Epub 2011 Oct 13.
The purpose of this study was to generate, by real-time PCR, a quantitative expression level profile of the 19 human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A and 2B, in 26 adult and 3 fetal tissues, for better understanding of their roles in xenobiotic and endobiotic metabolism. Adult liver contained the highest level of combined UGTs mRNA, and UGT2B4 was the most abundant isoform in this tissue (40% of total). Other well expressed hepatic UGTs, in decreasing order of mRNA level, were 1A9, 2B7, 1A4, 2B10, 1A1, 1A6, 2B11, 2B15, 1A3, 2A3, 2B17 and 2B28. UGT2B4 was by far the most abundant isoform in the fetal liver (90% of total). The combined UGT mRNA expression in both adult and fetal olfactory epithelium was high, about 20% the adult hepatic level. Interestingly, a large developmental change was found in this tissue from high UGT2A1 and UGT2A2 expression in the fetus to UGT1A6 in the adult. The most abundantly expressed UGTs in the small intestine were 2A3, 1A10, 1A1, 1A6 and 2B7, while 1A10 and 2A3 predominated in the colon. The results provide the most comprehensive data to date on the tissue distribution of the human UGTs.
本研究的目的是通过实时聚合酶链反应（PCR），生成19种人尿苷二磷酸葡萄糖醛酸转移酶（UGTs）（1A、2A和2B亚家族）在26种成人组织和3种胎儿组织中的定量表达水平图谱，以更好地了解它们在异生物质和内源性物质代谢中的作用。成人肝脏中UGTs mRNA的总水平最高，UGT2B4是该组织中最丰富的亚型（占总量的40%）。其他在肝脏中高表达的UGTs，按mRNA水平从高到低依次为1A9、2B7、1A4、2B10、1A1、1A6、2B11、2B15、1A3、2A3、2B17和2B28。UGT2B4是胎儿肝脏中迄今为止最丰富的亚型（占总量的90%）。成人和胎儿嗅觉上皮中UGT mRNA的总表达水平都很高，约为成人肝脏水平的20%。有趣的是，在该组织中发现了较大的发育变化，从胎儿期高表达的UGT2A1和UGT2A2转变为成人期的UGT1A6。小肠中表达最丰富的UGTs是2A3、1A10、1A1、1A6和2B7，而1A10和2A3在结肠中占主导地位。这些结果提供了迄今为止关于人UGTs组织分布最全面的数据。
