ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Sex-specific effects of gut microbiome on shaping bile acid metabolism.bioRxiv : the preprint server for biology · 2024Article
- Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury.Communications biology · 2024Article
- 18β-Glycyrrhetinic Acid Protects against Cholestatic Liver Injury in Bile Duct-Ligated Rats.Antioxidants (Basel, Switzerland) · 2022Article
- Oltipraz ameliorates the progression of steatohepatitis in Nrf2-null mice fed a high-fat diet.Journal of clinical biochemistry and nutrition · 2022Article
- Nrf2 deficiency causes hepatocyte dedifferentiation and reduced albumin production in an experimental extrahepatic cholestasis model.PloS one · 2022Article
- Bicyclol Alleviates Signs of BDL-Induced Cholestasis by Regulating Bile Acids and Autophagy-Mediated HMGB1/p62/Nrf2 Pathway.Frontiers in pharmacology · 2021Article
- Effects of ablation and activation of Nrf2 on bile acid homeostasis in male mice.Toxicology and applied pharmacology · 2020Article
- Cholestasis Differentially Affects Liver Connexins.International journal of molecular sciences · 2020Article
- Intestinal Absorption of Bile Acids in Health and Disease.Comprehensive Physiology · 2019Review
- Cholestatic liver disease results increased production of reactive aldehydes and an atypical periportal hepatic antioxidant response.Free radical biology & medicine · 2019Article
- Hepatic Autophagy Deficiency Compromises Farnesoid X Receptor Functionality and Causes Cholestatic Injury.Hepatology (Baltimore, Md.) · 2019Article
- Mechanistic insights into geniposide regulation of bile salt export pump (BSEP) expression.RSC advances · 2018Article
- Post-hepatectomy liver regeneration in the context of bile acid homeostasis and the gut-liver signaling axis.Journal of clinical and translational research · 2018Article
- Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Organic Solute Transporter α-β Protects Ileal Enterocytes From Bile Acid-Induced Injury.Cellular and molecular gastroenterology and hepatology · 2018Article
- Mechanisms of Triptolide-Induced Hepatotoxicity and Protective Effect of Combined Use of Isoliquiritigenin: Possible Roles of Nrf2 and Hepatic Transporters.Frontiers in pharmacology · 2018Article
- Hepatoprotective Activity of the Ethanolic Extract ofEvidence-based complementary and alternative medicine : eCAM · 2018Article
- Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice.Frontiers in pharmacology · 2017Article
- Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish.Hepatology (Baltimore, Md.) · 2016Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2(-/-) mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2(-/-) compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2(-/-) mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.