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Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues

UDP‐glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that play important roles in the detoxification of endogenous and exogenous substrates. The 22 human UGTs belong to four families (UGT1, UGT2, UGT3, and UGT8) and differ in their expression, substrate specificity, UDP‐sugar p...

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Autores principales: Zhou, Lucas, Montalvo, Abelardo D., Collins, Joseph M., Wang, Danxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659769/
https://www.ncbi.nlm.nih.gov/pubmed/37983911
http://dx.doi.org/10.1002/prp2.1154
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author Zhou, Lucas
Montalvo, Abelardo D.
Collins, Joseph M.
Wang, Danxin
author_facet Zhou, Lucas
Montalvo, Abelardo D.
Collins, Joseph M.
Wang, Danxin
author_sort Zhou, Lucas
collection PubMed
description UDP‐glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that play important roles in the detoxification of endogenous and exogenous substrates. The 22 human UGTs belong to four families (UGT1, UGT2, UGT3, and UGT8) and differ in their expression, substrate specificity, UDP‐sugar preference, and physiological functions. Differential expression/activity of the UGTs contributes to interperson variability in drug responses and toxicity, hormone homeostasis, and disease/cancer risks. However, in normal tissues, the tissue‐specific expression profiles and transcriptional regulation of the UGTs are still not fully understood. In this study, we comprehensively analyzed the transcriptome of 22 UGTs in 54 human tissues/regions using RNAseq data from GTEx. We then validated the findings in the liver and small intestine samples using real‐time PCR. Our results showed large interindividual variability across tissues in the expression of each UGT and the overall composition of UGT pools, consisting of different UGTs and their splice isoforms. Our results also revealed coexpression of the UGTs, Cytochrome P450s, and many transcription factors in the liver, suggesting potential coregulation or functional coordination. Our results provide the groundwork for future studies to detail further the regulation of the expression and activity of the UGTs.
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spelling pubmed-106597692023-11-20 Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues Zhou, Lucas Montalvo, Abelardo D. Collins, Joseph M. Wang, Danxin Pharmacol Res Perspect Original Articles UDP‐glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that play important roles in the detoxification of endogenous and exogenous substrates. The 22 human UGTs belong to four families (UGT1, UGT2, UGT3, and UGT8) and differ in their expression, substrate specificity, UDP‐sugar preference, and physiological functions. Differential expression/activity of the UGTs contributes to interperson variability in drug responses and toxicity, hormone homeostasis, and disease/cancer risks. However, in normal tissues, the tissue‐specific expression profiles and transcriptional regulation of the UGTs are still not fully understood. In this study, we comprehensively analyzed the transcriptome of 22 UGTs in 54 human tissues/regions using RNAseq data from GTEx. We then validated the findings in the liver and small intestine samples using real‐time PCR. Our results showed large interindividual variability across tissues in the expression of each UGT and the overall composition of UGT pools, consisting of different UGTs and their splice isoforms. Our results also revealed coexpression of the UGTs, Cytochrome P450s, and many transcription factors in the liver, suggesting potential coregulation or functional coordination. Our results provide the groundwork for future studies to detail further the regulation of the expression and activity of the UGTs. John Wiley and Sons Inc. 2023-11-20 /pmc/articles/PMC10659769/ /pubmed/37983911 http://dx.doi.org/10.1002/prp2.1154 Text en © 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Zhou, Lucas
Montalvo, Abelardo D.
Collins, Joseph M.
Wang, Danxin
Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues
title Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues
title_full Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues
title_fullStr Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues
title_full_unstemmed Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues
title_short Quantitative analysis of the UDP‐glucuronosyltransferase transcriptome in human tissues
title_sort quantitative analysis of the udp‐glucuronosyltransferase transcriptome in human tissues
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659769/
https://www.ncbi.nlm.nih.gov/pubmed/37983911
http://dx.doi.org/10.1002/prp2.1154
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