The role of bile acids in cholestatic liver injury.

Ann Transl Med

Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT 06520, USA.

Published: April 2021

Clinical disorders that impair bile flow result in retention of bile acids and cholestatic liver injury, characterized by parenchymal cell death, bile duct proliferation, liver inflammation and fibrosis. However, the pathogenic role of bile acids in the development of cholestatic liver injury remains incompletely understood. In this review, we summarize the current understanding of this process focusing on the experimental and clinical evidence for direct effects of bile acids on each major cellular component of the liver: hepatocytes, cholangiocytes, stellate cells and immune cells. During cholestasis bile acids accumulated in the liver, causing oxidative stress and mitochondrial injury in hepatocytes. The stressed hepatocytes respond by releasing inflammatory cytokines through activation of specific signaling pathways and transcription factors. The recruited neutrophils and other immune cells then cause parenchymal cell death. In addition, bile acids also stimulate the proliferation of cholangiocytes and stellate cells that are responsible for bile duct proliferation and liver fibrosis. This review explores the evidence for bile acid involvement in these phenomena. The role of bile acid receptors, TGR5, FXR and the sphingosine-1-phosphate receptor 2 and the inflammasome are also examined. We hope that better understanding of these pathologic effects will facilitate new strategies for treating cholestatic liver injury.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106037PMC
http://dx.doi.org/10.21037/atm-20-5110DOI Listing

Publication Analysis

Top Keywords

bile acids
24
cholestatic liver
16
liver injury
16
role bile
12
bile
10
acids cholestatic
8
liver
8
parenchymal cell
8
cell death
8
bile duct
8

Similar Publications

Bile acids (BAs), not only promote the absorption of fat-soluble nutrients and regulate the metabolism of multiple substances but also have a potential role as diagnostic and prognostic indicators in a variety of diseases such as cholestasis, hepatocellular carcinoma, and diabetes mellitus. Here, a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of 50 BAs was developed and validated. Sample preparation included internal standard spiking, followed by protein precipitation, centrifugation, solvent evaporation, and reconstitution.

View Article and Find Full Text PDF

A novel multi-organ male model of alcohol-induced acute-on-chronic liver failure reveals NET-mediated hepatocellular death which is prevented by RIPK3 inhibition.

Cell Mol Gastroenterol Hepatol

December 2024

Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Broad Institute, Cambridge, MA. Electronic address:

Background And Aims: Alcohol abuse is the most frequent precipitating factor of acute-on-chronic liver failure (ACLF). We aimed at developing an alcohol-induced ACLF model and dissecting its underlying molecular mechanisms.

Methods: ACLF was triggered by a single alcohol binge (5g/Kg) in a bile duct ligation (BDL) liver fibrosis murine model.

View Article and Find Full Text PDF

Polysaccharides from Yupingfeng granules ameliorated cyclophosphamide-induced immune injury by protecting intestinal barrier.

Int Immunopharmacol

December 2024

Sinopharm Group Guangdong Medi-World Pharmaceutical Co., Ltd., Guangzhou, China.

Immune injury is the main side effect caused by cyclophosphamide and the disruption of the intestinal barrier may be an important cause. Yupingfeng granules have been reported to have immunomodulatory effects and polysaccharides are important components of them. This study aimed to investigate the ameliorative effect of polysaccharides from Yupingfeng granules (YPFP) on cyclophosphamide induced immune injury and reveal their potential mechanisms based on its protective effect on the intestine.

View Article and Find Full Text PDF

Study on the Mechanism of Bifidobacterium animalis subsp. lactis F1-3-2 Regulating Bile Acid Metabolism Through TMA-TMAO Pathway to Improve Atherosclerosis.

Probiotics Antimicrob Proteins

December 2024

Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, 266100, Shandong, China.

Atherosclerosis is a major cause of cardiovascular disease (CVD). The trimethylamine (TMA)-trimethylamine N-oxide (TMAO) pathway is a key crossover pathway highly associated with diet, gut microbiome, and atherosclerosis. The Bifidobacterium animalis subsp.

View Article and Find Full Text PDF

Background: Yes-associated protein 1 (YAP1) regulates the survival, proliferation, and stemness of cells, and contributes to the development of metabolic dysfunction associated fatty liver disease (MAFLD). However, the regulatory role of intestinal YAP1 in MAFLD still remains unclear.

Methods: Terminal ileal specimens were used to compare intestinal YAP1 activation in patients with and without MAFLD.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!