ArticleHepatology (Baltimore, Md.)2017
The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 250 citations in OpenAlex.
- LncRNA H19 as a key regulator in biliary atresia: insights into pathogenesis and potential therapeutic targets.Annals of medicine · 2026Review
- Alcohol-related liver disease disrupts bile acid homeostasis and gut microbial bile acid metabolism.JHEP reports : innovation in hepatology · 2026Article
- Alveolar Type 2 Cell Dysfunction Is Associated with Bile Acid Alterations in Experimental Hepatopulmonary Syndrome.American journal of respiratory cell and molecular biology · 2026Article
- Gut microbiome and bile acid metabolism in liver disease: Mechanisms, clinical implications, and therapeutic opportunities.Pharmacological reviews · 2026Review
- Targeting SPHK1 by 8-HETrE attenuates MASH-Driven fibrosis via restoration of hepatic stellate cell mitochondrial dynamics.Cell biology and toxicology · 2026Article
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- SphK1/S1P signaling-mediated crosstalk between pancreatic acinar cell and macrophage M1 polarization aggravates acute pancreatitis progression.International journal of biological sciences · 2026Article
- The interplay between bile acid metabolism and gut microbiome in biliary tract cancers.Frontiers in microbiomes · 2026Review
- Senkyunolide A interrupts TRAF6-HDAC3 interaction to epigenetically suppress c-MYC and attenuate cholestatic liver injury.Journal of advanced research · 2026Article
- Glycochenodeoxycholic acid promotes hepatocarcinogenesis by inducing hepatic progenitor cell differentiation into cancer-associated fibroblasts via sphingosine-1-phosphate receptor 2 signalling.Biomarker research · 2025Article
- Cholangiocyte-derived exosomal miR-381-3p promotes hepatic stellate cell activation and cholestatic liver fibrosis via targeting Klf6.Regenerative therapy · 2025Article
- Hepatic protein kinase Cβ antagonizing p38American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Gut microbiota and microbial metabolites for osteoporosis.Gut microbes · 2025Review
- Senkyunolide A ameliorates cholestatic liver fibrosis by controlling CLCC1-mediated endoplasmic reticulum CaActa pharmacologica Sinica · 2025Article
- Anti-fibrotic and anti-inflammatory effects of D-limonene in improving liver cirrhosis induced by bile duct ligation in male rat.BMC pharmacology & toxicology · 2025Article
- Sphingosine kinase 2 deficiency impairs VLDL secretion by inhibiting mTORC2 phosphorylation and activating chaperone-mediated autophagy.Cell death and differentiation · 2025Article
- Central role for cholangiocyte pathobiology in cholestatic liver diseases.Hepatology (Baltimore, Md.) · 2025Review
- Taurochenodeoxycholic acid as a sensitive stratification marker for HBV-associated hepatic cirrhosis status has a hepatoprotective effect.Scientific reports · 2025Article
- Multifaceted Interactions Between Bile Acids, Their Receptors, and MASH: From Molecular Mechanisms to Clinical Therapeutics.Molecules (Basel, Switzerland) · 2025Review
- Conjugated bile acids promote metabolic dysfunction-associated steatotic liver disease through inducing nuclear translocation of sphingosine-1-phosphate receptor 2 to disrupt peroxisome proliferator-activated receptor alpha.Cell communication and signaling : CCS · 2025Article
75 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially for large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the protein kinase B (AKT) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways through sphingosine 1-phosphate receptor (S1PR) 2 in hepatocytes and cholangiocarcinoma cells. It also has been reported that taurocholate (TCA) promotes large cholangiocyte proliferation and protects cholangiocytes from bile duct ligation (BDL)-induced apoptosis. However, the role of S1PR2 in bile-acid-mediated cholangiocyte proliferation and cholestatic liver injury has not been elucidated. Here, we report that S1PR2 is the predominant S1PR expressed in cholangiocytes. Both TCA- and sphingosine-1-phosphate (S1P)-induced activation of ERK1/2 and AKT were inhibited by JTE-013, a specific antagonist of S1PR2, in cholangiocytes. In addition, TCA- and S1P-induced cell proliferation and migration were inhibited by JTE-013 and a specific short hairpin RNA of S1PR2, as well as chemical inhibitors of ERK1/2 and AKT in mouse cholangiocytes. In BDL mice, expression of S1PR2 was up-regulated in whole liver and cholangiocytes. S1PR2 deficiency significantly reduced BDL-induced cholangiocyte proliferation and cholestatic injury, as indicated by significant reductions in inflammation and liver fibrosis in S1PR2 knockout mice. Treatment of BDL mice with JTE-013 significantly reduced total bile acid levels in serum and cholestatic liver injury.
conclusionThis study suggests that CBA-induced activation of S1PR2-mediated signaling pathways plays a critical role in obstructive cholestasis and may represent a novel therapeutic target for cholestatic liver diseases. (Hepatology 2017;65:2005-2018).
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