ArticleGastroenterology2018
Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis.
Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- PBPK Modeling of Varenicline: Relating Variable Pharmacokinetics to Genomics.European journal of drug metabolism and pharmacokinetics · 2026Article
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization.Nature communications · 2026Article
- Review
- Decoding the role of H19 in cholestatic liver injury using snRNA-seq, spatial transcriptomics, and machine learning-based disease prediction.Cell & bioscience · 2026Article
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- Decoding the Role of H19 in Cholestatic Liver Injury Using snRNA-seq, Spatial Transcriptomics, and Machine Learning-Based Disease Prediction.Research square · 2026Article
- Aluminum adjuvant promotes liver inflammation and fibrosis in mice: A novel approach to establish a liver fibrosis animal model.Liver research (Beijing, China) · 2025Article
- Targeting the ceramidase ACER3 attenuates cholestasis in mice by mitigating bile acid overload via unsaturated ceramide-mediated LXRβ signaling transduction.Nature communications · 2025Article
- Organic anion transporting polypeptides: Pharmacology, toxicology, structure, and transport mechanisms.Pharmacological reviews · 2025Review
- STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis.Journal of clinical and translational hepatology · 2024Article
- Transporter Protein Expression of Corneal Epithelium in Rabbit and Porcine: Evaluation of Models for Ocular Drug Transport Study.Molecular pharmaceutics · 2024Article
- Article
- Melatonin attenuates cholestatic liver injury via inhibition of the inflammatory response.Molecular and cellular biochemistry · 2023Article
- Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NFκB/Caspase-1/GSDMD signaling in cholestasis.Cell death discovery · 2023Article
- Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans.Cellular and molecular gastroenterology and hepatology · 2023Article
- Hepatic Aquaporin 10 Expression Is Downregulated by Activated NFκB Signaling in Human Obstructive Cholestasis.Gastro hep advances · 2023Article
- SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface.JCI insight · 2022Article
- Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis.Frontiers in pharmacology · 2022Article
- Overview of Drug Transporters in Human Placenta.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsBile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis.
methodsWe measured levels of OATP3A1 protein and messenger RNA and localized the protein in liver tissues from 22 patients with cholestasis and 21 patients without cholestasis, using real-time quantitative polymerase chain reaction, immunoblot, and immunofluorescence analyses. We performed experiments with Slco3a1-knockout and C57BL/6J (control) mice. Mice and Sprague-Dawley rats underwent bile duct ligation (BDL) or a sham operation. Some mice were placed on a 1% cholic acid (CA) diet to induce cholestasis or on a control diet. Serum and liver tissues were collected and analyzed; hepatic levels of bile acids and 7-α-C4 were measured using liquid chromatography/mass spectrometry. Human primary hepatocytes and hepatoma (PLC/PRF/5) cell lines were used to study mechanisms that regulate OATP3A1 expression and transport.
resultsHepatic levels of OATP3A1 messenger RNA and protein were significantly increased in liver tissues from patients with cholestasis and from rodents with BDL or 1% CA diet-induced cholestasis. Levels of fibroblast growth factor 19 (FGF19, FGF15 in rodents) were also increased in liver tissues from patients and rodents with cholestasis. FGF19 signaling activated the Sp1 transcription factor and nuclear factor κB to increase expression of OATP3A1 in hepatocytes; we found binding sites for these factors in the SLCO3A1 promoter. Slco3a1-knockout mice had shorter survival times and increased hepatic levels of bile acid, and they developed more liver injury after the 1% CA diet or BDL than control mice. In hepatoma cell lines, we found OATP3A1 to take prostaglandin E2 and thyroxine into cells and efflux bile acids.
conclusionsWe found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.
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