ArticleThe Journal of clinical investigation1998
Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 262 citations in OpenAlex.
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- Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease.Hepatology (Baltimore, Md.) · 2025Review
- Deciphering the cell type-specific and zonal distribution of drug-metabolizing enzymes, transporters, and transcription factors in livers of mice using single-cell transcriptomics.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Intraduodenal fecal microbiota transplantation ameliorates gut atrophy and cholestasis in a novel parenteral nutrition piglet model.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Interleukin 1 β suppresses bile acid-induced BSEP expression via a CXCR2-dependent feedback mechanism.PloS one · 2024Article
- Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis.Nature communications · 2023Article
- Review
- Transcription networks in liver development and acute liver failure.Liver research (Beijing, China) · 2023Review
- Lower systemic inflammation is associated with gut firmicutes dominance and reduced liver injury in a novel ambulatory model of parenteral nutrition.Annals of medicine · 2022Article
- Review
- Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology.Nature reviews. Gastroenterology & hepatology · 2022Review
- Pathophysiology of sepsis-induced cholestasis: A review.JGH open : an open access journal of gastroenterology and hepatology · 2022Review
- Beyond lipids: Novel mechanisms for parenteral nutrition-associated liver disease.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2022Review
- The Specific Bile Acid Profile of Shock: A Hypothesis Generating Appraisal of the Literature.Journal of clinical medicine · 2020Article
- Mechanisms of Parenteral Nutrition-Associated Liver and Gut Injury.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2020Review
- Advances in the Study of the Potential Hepatotoxic Components and Mechanism ofEvidence-based complementary and alternative medicine : eCAM · 2020Review
- Role of Bile Acids and Gut Microbiota in Parenteral Nutrition Associated Injury.Journal of human nutrition (Carson City, Nev.) · 2020Article
- Effects of Endotoxin on Type 3 Inositol 1,4,5-Trisphosphate Receptor in Human Cholangiocytes.Hepatology (Baltimore, Md.) · 2019Article
- Role of the Gut⁻Liver Axis in Driving Parenteral Nutrition-Associated Injury.Children (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Sodium-dependent uptake of bile acids across the hepatic basolateral membrane is rapidly and profoundly diminished during sepsis, thus contributing to the pathogenesis of sepsis-associated cholestasis. This effect is mediated by endotoxin or effector cytokines, which reduce expression of several hepatobiliary transporters, including the sodium-dependent bile acid transporter gene, ntcp. We test here the hypothesis that endotoxin treatment leads to impaired binding activity of ntcp promoter trans-acting factors, resulting in reduction of ntcp mRNA expression. After endotoxin administration, ntcp mRNA levels reached their nadir by 16 h, and nuclear run-on assays demonstrated a marked reduction in ntcp gene transcription. At 16 h after treatment, nuclear binding activities of two key factors that transactivate the ntcp promoter, hepatocyte nuclear factor (HNF) 1 and Footprint B binding protein (FpB BP), decreased to 44 and 47% of pretreatment levels, respectively, while levels of the other known ntcp promoter transactivator, signal transducer and activator of transcription 5, were unaffected. In contrast, the universal inflammatory response factors nuclear factor kappaB and activating protein 1 were both upregulated significantly. Examination of nuclear extracts obtained at sequential time points revealed that the maximal decrease in nuclear activities of both HNF1 and FpB BP preceded the nadir of ntcp mRNA expression by 6-10 h. Furthermore, these two nuclear factors returned towards normal levels before the recovery of ntcp mRNA levels observed by 48 h. Since HNF1alpha mRNA levels were unchanged at all time points, HNF1 is likely to be regulated posttranscriptionally by endotoxin. We conclude that the downregulation of ntcp gene expression by endotoxin is mediated at the level of transcription through tandem reductions in the nuclear binding activity of two critical transcription factors. These findings provide new insight into the coordinated downregulation of hepatobiliary transporters during sepsis.
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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.