Hepatic expression of transcription factors affecting developmental regulation of UGT1A1 in the Han Chinese population
| العنوان: | Hepatic expression of transcription factors affecting developmental regulation of UGT1A1 in the Han Chinese population |
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| المؤلفون: | Lirong Zhang, Quan-cheng Kan, Shu-jie Wang, Pei Wang, Hong-zheng Bi, Xiang-Guang Meng, Jiang-feng Li, Yali Nie, Liang Yan, Hang He |
| المصدر: | European Journal of Clinical Pharmacology. 73:29-37 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Han chinese, Glucuronosyltransferase, Genotype, Bilirubin, Pharmacology toxicology, Glucuronidation, Gestational Age, digestive system, 030226 pharmacology & pharmacy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Asian People, Humans, Pharmacology (medical), RNA, Messenger, Transcription factor, Aged, Pharmacology, Genetics, Polymorphism, Genetic, biology, Infant, General Medicine, Middle Aged, 030104 developmental biology, Liver, chemistry, Child, Preschool, biology.protein, Female, Transcription Factors |
| الوصف: | Complete or partial inactivity of UGT1A1, the unique enzyme responsible for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We investigated the dynamic expression of UGT1A1, and that of the transcription factors (TFs) involved in its developmental regulation, during human hepatic growth in Han Chinese individuals.Eighty-eight prenatal, pediatric, and adult liver samples were obtained from Han Chinese individuals. Quantitative real-time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc. UGT1A1 protein levels and metabolic activity were determined by western blotting and high-performance liquid chromatography. Direct sequencing was employed to genotype UGT1A1*6 (211G˃A) and UGT1A1*28 (TA6˃TA7) polymorphisms.UGT1A1 expression was minimal in prenatal samples, but significantly elevated during pediatric and adult stages. mRNA and protein levels and metabolic activity were prominently increased (120-, 20-, and 10-fold, respectively) in pediatric and adult livers compared to prenatal samples. Furthermore, expression did not differ appreciably between pediatric and adult periods. Dynamic expression of TFs, including PXR, CAR, HNF1A, HNF4A, and PPARA, was consistent with UGT1A1 levels at each developmental stage. A pronounced correlation between expression of these TFs and that of UGT1A1 (P 0.001) was observed. Moreover, UGT1A1*6 and UGT1A1*28 polymorphisms reduced levels of UGT1A1 by up to 40-60 %.Hepatic expression of transcription factors is associated with developmental regulation of UGT1A1 in the Han Chinese population. Moreover, UGT1A1 polymorphisms are associated with reduced expression of UGT1A1 mRNA and protein, as well as enzyme activity. |
| تدمد: | 1432-1041 0031-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::73b13e16e09c6d3b8671c9ac8963aeb0Test https://doi.org/10.1007/s00228-016-2137-7Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....73b13e16e09c6d3b8671c9ac8963aeb0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321041 00316970 |
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