ArticleHepatology (Baltimore, Md.)2020
Impaired Bile Secretion Promotes Hepatobiliary Injury in Sickle Cell Disease.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Loss of energy homeostasis contributes to hepatic damage development in sickle cell disease.Molecular metabolism · 2026Article
- Hepatobiliary complications in patients with sickle cell disease: A 30-year review of 1009 patients.Hepatology communications · 2025Article
- GBT1118, a Voxelotor Analog, Ameliorates Hepatopathy in Sickle Cell Disease.Medicina (Kaunas, Lithuania) · 2024Article
- Hemoglobin scavenger receptor CD163 as a potential biomarker of hemolysis-induced hepatobiliary injury in sickle cell disease.American journal of physiology. Cell physiology · 2024Article
- Impaired hemoglobin clearance by sinusoidal endothelium promotes vaso-occlusion and liver injury in sickle cell disease.Haematologica · 2024Article
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Long-Term L-Glutamine Treatment Reduces Hemolysis without Ameliorating Hepatic Vaso-Occlusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease.Biomedicines · 2023Article
- Article
- Molecular mechanisms of hepatic dysfunction in sickle cell disease: lessons from Townes mouse model.American journal of physiology. Cell physiology · 2022Review
- Intravital imaging reveals inflammation as a dominant pathophysiology of age-related hepatovascular changes.American journal of physiology. Cell physiology · 2022Article
- Urine metabolomics and microbiome analyses reveal the mechanism of anti-tuberculosis drug-induced liver injury, as assessed for causality using the updated RUCAM: A prospective study.Frontiers in immunology · 2022Article
- Intravital Imaging of Hepatic Blood Biliary Barrier in Live Mice.Current protocols · 2021Article
- Article
- Drag-reducing polymers improve hepatic vaso-occlusion in SCD mice.Blood advances · 2020Article
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsHepatic crisis is an emergent complication affecting patients with sickle cell disease (SCD); however, the molecular mechanism of sickle cell hepatobiliary injury remains poorly understood. Using the knock-in humanized mouse model of SCD and SCD patient blood, we sought to mechanistically characterize SCD-associated hepato-pathophysiology applying our recently developed quantitative liver intravital imaging, RNA sequence analysis, and biochemical approaches. APPROACH AND
resultsSCD mice manifested sinusoidal ischemia, progressive hepatomegaly, liver injury, hyperbilirubinemia, and increased ductular reaction under basal conditions. Nuclear factor kappa B (NF-κB) activation in the liver of SCD mice inhibited farnesoid X receptor (FXR) signaling and its downstream targets, leading to loss of canalicular bile transport and altered bile acid pool. Intravital imaging revealed impaired bile secretion into the bile canaliculi, which was secondary to loss of canalicular bile transport and bile acid metabolism, leading to intrahepatic bile accumulation in SCD mouse liver. Blocking NF-κB activation rescued FXR signaling and partially ameliorated liver injury and sinusoidal ischemia in SCD mice.
conclusionsThese findings identify that NF-κB/FXR-dependent impaired bile secretion promotes intrahepatic bile accumulation, which contributes to hepatobiliary injury of SCD. Improved understanding of these processes could potentially benefit the development of therapies to treat sickle cell hepatic crisis.
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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.