Affinage

Showing ABCB11 — BSEP is a alias.

ABCB11

Bile salt export pump · UniProt O95342

Length
1321 aa
Mass
146.4 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCB11 (BSEP/Spgp) is the ATP-dependent canalicular transporter that constitutes the rate-limiting step for hepatocyte secretion of monoanionic bile salts into bile, driving overall bile flow and biliary lipid secretion (PMID:10648470, PMID:14570929). Reconstituted in vitro and in double-transfected polarized cells, it mediates vectorial basal-to-apical bile salt transport in concert with the uptake transporter NTCP, preferring unconjugated and glycine-conjugated bile salts and also handling non-bile-acid substrates such as pravastatin (PMID:15901796, PMID:16474011). Genetic ablation establishes BSEP as the primary but not sole canalicular bile acid pump, with residual output sustained by tetrahydroxylated bile acids and an alternative Mdr1/P-glycoprotein-mediated pathway (PMID:11172067, PMID:16156672). Its activity is tuned at the membrane by cholesterol content, which raises transport Vmax (PMID:19520776, PMID:24711118). BSEP biogenesis and surface residence are tightly controlled: at least two N-linked glycans are required for stability and apical targeting, and surface protein is removed by short-chain ubiquitination and proteasomal degradation, a process accelerated by disease mutations and slowed by 4-phenylbutyrate (PMID:17082223, PMID:18829893). Surface abundance is further set by dynamic vesicular retrieval and insertion governed by osmolarity acting through Fyn kinase and NADPH-oxidase-derived ROS, by cAMP/PKA-stimulated insertion, and by LKB1/AMPK-dependent microtubule trafficking through the rab11a–myosin Vb recycling endosome (PMID:12702498, PMID:11230729, PMID:22057277, PMID:24643070). Mutations in ABCB11 cause progressive (PFIC2) and benign recurrent (BRIC2) intrahepatic cholestasis, with severity tracking the degree of misprocessing, accelerated degradation, and loss of plasma-membrane expression (PMID:15791618, PMID:17855769, PMID:19101985, PMID:16039748). Beyond cholestasis, BSEP deficiency impairs mitochondrial fatty acid β-oxidation and, through accumulation of FXR-antagonist bile acids and loss of FXR signaling, promotes hepatocarcinogenesis (PMID:22619174, PMID:34410012).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2000 High

    Established that BSEP is a bona fide ATP-dependent bile salt transporter and dissected how a co-secreted compound exerts trans-inhibition only after Mrp2-dependent biliary delivery.

    Evidence ATP-dependent vesicle transport assays in Bsep/Mrp2-expressing Sf9 cells and rat canalicular membrane vesicles with inhibitor panels

    PMID:10648470

    Open questions at the time
    • Did not resolve transport stoichiometry or structural basis of substrate recognition
    • Mechanism of E217G internalization not addressed at this stage
  2. 2001 High

    Defined BSEP's in vivo role by showing knockout causes intrahepatic cholestasis yet retains partial bile salt output, revealing BSEP is the primary but not exclusive canalicular bile acid transporter.

    Evidence Targeted Abcb11 knockout mice with bile collection and HPLC composition analysis

    PMID:11172067

    Open questions at the time
    • Identity of the alternative transporter unresolved at this point
    • Did not address human phenotype correspondence
  3. 2001 Medium

    Showed that BSEP surface abundance is dynamically set by membrane retrieval/insertion rather than fixed, linking osmolarity to bile flow.

    Evidence Immunohistochemistry and confocal microscopy in perfused rat liver under defined osmotic conditions

    PMID:11230729

    Open questions at the time
    • Signaling intermediates linking osmolarity to retrieval not identified
    • Single lab, localization-based readout
  4. 2003 High

    Demonstrated cAMP-stimulated vesicular insertion of BSEP and identified endocytic internalization as a reversible cholestatic mechanism.

    Evidence Confocal microscopy, Western blot, and hepatocyte couplet transport assays in rat liver with Mrp2-deficient controls

    PMID:12702498

    Open questions at the time
    • Endocytic machinery components not identified
    • Did not define the kinase cascade downstream of cAMP
  5. 2003 High

    Established ABCB11 as rate-limiting for hepatobiliary bile salt secretion with downstream FXR/SHP and energy-homeostasis consequences.

    Evidence Two independent Abcb11 transgenic mouse lines with bile analysis, hepatic gene expression, and lithogenic diet challenge

    PMID:14570929

    Open questions at the time
    • Mechanism linking bile salt pool to systemic energy metabolism only correlative
    • FXR ligand changes inferred from pool composition
  6. 2005 High

    Defined the molecular basis of PFIC2 mutations E297G/D482G as trafficking defects (ER retention, core glycosylation, proteasomal degradation) rather than intrinsic transport loss.

    Evidence Site-directed mutagenesis in HEK293/MDCK cells with glycosylation analysis, transport assays, and MG132 proteasome inhibition

    PMID:15791618

    Open questions at the time
    • E3 ligase mediating degradation not identified
    • Did not test pharmacological chaperone rescue
  7. 2005 High

    Broadened BSEP substrate range to non-bile-acid compounds and quantified statin interactions relevant to drug-induced cholestasis.

    Evidence ATP-dependent vesicle uptake assays with kinetic and competitive inhibition analysis across human and rat orthologs

    PMID:15901796

    Open questions at the time
    • In vivo relevance of pravastatin transport not established
    • Structural basis of statin inhibition unknown
  8. 2005 Medium

    Provided direct in vitro evidence that P-glycoprotein/Mdr1 is the compensatory alternative bile acid transporter upregulated in BSEP deficiency.

    Evidence Western blotting of Abcb11 KO mice plus ATP-dependent bile acid transport in Mdr1-overexpressing membrane vesicles

    PMID:16156672

    Open questions at the time
    • Physiological contribution in vivo not quantified
    • Single lab
  9. 2005 Medium

    Linked partial loss-of-function transport defects to the milder BRIC2 phenotype, distinguishing it from PFIC2 by preserved hepatic BSEP expression.

    Evidence ABCB11 sequencing with taurocholate transport assays in Sf9 cells and liver biopsy immunohistochemistry

    PMID:16039748

    Open questions at the time
    • Limited to two mutations
    • Single patient/lab
  10. 2006 High

    Reconstituted vectorial transcellular bile salt transport and defined BSEP substrate preference, establishing the NTCP-BSEP axis.

    Evidence Double-transfected LLC-PK1 cells with directional flux and substrate clearance measurements

    PMID:16474011

    Open questions at the time
    • Did not address regulation of the coupled system
    • Lithocholate handling left unexplained mechanistically
  11. 2006 High

    Established N-linked glycosylation as a determinant of BSEP stability, trafficking, and function, with at least two glycans required for apical expression.

    Evidence Site-directed mutagenesis of glycosylation sites in rat Bsep-YFP in MDCK cells with half-life, localization, glycosidase, and transport readouts

    PMID:17082223

    Open questions at the time
    • Which glycan-recognizing quality-control machinery acts on BSEP not identified
    • Did not address glycan role in human disease variants
  12. 2006 Medium

    Identified oxidative stress as an internalizing stimulus acting through a Ca2+/PKC pathway reversible by PKA, with cytoskeletal involvement.

    Evidence Pro-oxidant treatment of rat hepatocyte couplets with kinase inhibitors/activators, Ca2+ chelation, and Bsep immunofluorescence

    PMID:16452108

    Open questions at the time
    • Molecular link between PKC and the endocytic machinery undefined
    • Pharmacological inhibitors lack absolute specificity
  13. 2007 High

    Connected clinical severity to the level of BSEP plasma-membrane expression and demonstrated ubiquitin-dependent degradation with pharmacological chaperone rescue.

    Evidence Mutant rat Bsep in HEK293 cells with surface biotinylation, confocal imaging, MG132, and temperature/4PBA/butyrate rescue

    PMID:17855769

    Open questions at the time
    • Specific ubiquitin ligase not identified
    • Rat ortholog used as surrogate for human variants
  14. 2007 High

    Showed transport function declines in proportion to accelerated degradation and mapped the C-terminal tail as required for transport but not targeting.

    Evidence Mutant rat Bsep in MDCK cells with transport kinetics, half-life, and polarized localization

    PMID:17947449

    Open questions at the time
    • Structural role of the C-terminus in the transport cycle unresolved
    • Rat surrogate system
  15. 2007 Medium

    Identified TNF-α and IL-1β as mediators of zone-specific periportal BSEP downregulation in obstructive cholestasis.

    Evidence Bile duct ligation in rats with zonal immunofluorescence and cytokine neutralization

    PMID:17916651

    Open questions at the time
    • Intracellular signaling from cytokine to transporter loss not defined
    • Single lab
  16. 2008 High

    Directly demonstrated short-chain ubiquitination of cell-surface BSEP as the degradation signal, modulated by disease mutations and 4PBA.

    Evidence Ubiquitin modification assays in MDCK cells and rat canalicular vesicles with surface biotinylation, chimeric ubiquitin-BSEP, and 4PBA treatment

    PMID:18829893

    Open questions at the time
    • Responsible ubiquitin ligase and deubiquitinase unidentified
    • Recognition signal on BSEP not mapped
  17. 2009 High

    Systematically dissected ABCB11 mutations into pre-mRNA splicing defects versus protein ER-retention/degradation defects, with chaperone-rescuable subsets.

    Evidence Minigene splicing assays, CHO-K1 expression with ER colocalization, glycerol/temperature rescue, and transport assays across most known mutations

    PMID:19101985

    Open questions at the time
    • Did not test all mutants functionally for transport
    • In vivo splicing relevance inferred from minigenes
  18. 2009 Medium

    Identified membrane cholesterol as a positive kinetic modulator of BSEP transport across species and a partial rescuer of mutant activity.

    Evidence Sf9-expressed human/rat/mouse BSEP with cholesterol loading and kinetic transport assays

    PMID:19520776

    Open questions at the time
    • Molecular mechanism of cholesterol effect on the transport cycle unknown
    • Single lab
  19. 2010 Medium

    Revealed species-specific and mRNA-versus-protein discordant cytokine regulation of BSEP, cautioning against extrapolating rodent regulation to humans.

    Evidence Sandwich-cultured human and rat hepatocytes treated with TNF-α/IL-6/IL-1β with parallel mRNA and protein quantification

    PMID:20702406

    Open questions at the time
    • Post-transcriptional mechanism underlying protein increase not defined
    • Single lab
  20. 2011 High

    Established the Fyn kinase / NADPH-oxidase ROS / cortactin axis as the mechanism of hyperosmolarity-induced canalicular transporter retrieval.

    Evidence Perfused rat liver with Src-selective inhibitors, p47phox KO mice, ROS scavengers, Fyn knockdown, and cortactin phosphorylation assays

    PMID:22057277

    Open questions at the time
    • How cortactin phosphorylation drives the endocytic step mechanistically unresolved
    • Rat liver system
  21. 2012 Medium

    Showed that BSEP deficiency impairs mitochondrial long-chain fatty acid β-oxidation prior to overt cholestasis, linking bile salt secretion to lipid metabolism.

    Evidence Abcb11 KO C57BL/6J mice with lipid metabolism profiling, metabolomics, and gene expression analysis

    PMID:22619174

    Open questions at the time
    • Causal pathway from bile acid retention to β-oxidation suppression not mechanistically defined
    • Single lab
  22. 2013 Medium

    Achieved first heterologous purification of human BSEP and confirmed intrinsic ATP-binding of the isolated protein.

    Evidence Pichia pastoris expression, detergent screening, FSEC, and ATP-agarose binding

    PMID:23593265

    Open questions at the time
    • No full functional transport reconstitution reported
    • No structure determined
  23. 2014 High

    Defined LKB1/AMPK-dependent microtubule trafficking through the rab11a-myosin Vb recycling endosome as the route for canalicular BSEP delivery, separable from a cAMP/PKA pathway.

    Evidence Liver-specific LKB1 KO mice, collagen sandwich hepatocytes, live-cell imaging, FRAP, particle tracking, and pharmacological pathway dissection

    PMID:24643070

    Open questions at the time
    • Direct molecular link from AMPK to the trafficking machinery unresolved
    • Human hepatocyte confirmation not performed
  24. 2014 Medium

    Refined cholesterol modulation of BSEP across common variants and mutants, showing variant- and mutant-specific kinetic responses.

    Evidence Baculovirus-expressed BSEP variants/mutants in insect cells with cholesterol loading and Hanes-Woolf kinetic analysis

    PMID:24711118

    Open questions at the time
    • Mechanistic basis of variant-specific cholesterol sensitivity unknown
    • Single lab
  25. 2020 Medium

    Demonstrated a trafficking-competent but transport-dead PFIC2 mutant (T463I) in an ATP-binding motif that is pharmacologically rescuable by ivacaftor.

    Evidence 3D modelling, mutagenesis, expression in Can10 and MDCK/Ntcp cells, and ivacaftor treatment with transport assays

    PMID:32433800

    Open questions at the time
    • Direct structural confirmation of impaired ATP binding lacking
    • Single mutation, single lab
  26. 2021 Medium

    Established a causal chain from ABCB11 deficiency through accumulation of FXR-antagonist bile acids and loss of FXR signaling to hepatocarcinogenesis, reversible by FXR agonism.

    Evidence Longitudinal Abcb11-/- mice with histology, RNA-seq, bile acid profiling, FXR activity, and obeticholic acid rescue

    PMID:34410012

    Open questions at the time
    • Downstream FXR target genes driving transformation not pinpointed
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structure of human BSEP, the identity of the E3 ligase/deubiquitinase controlling its surface turnover, and the molecular coupling between trafficking signals (AMPK, Fyn/cortactin) and the endocytic/recycling machinery remain undefined.
  • No experimental structure of human BSEP in the corpus
  • Ubiquitin ligase mediating short-chain ubiquitination unidentified
  • Mechanistic link from retrieval signaling to membrane scission undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0005215 transporter activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 3 R-HSA-382551 Transport of small molecules 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-392499 Metabolism of proteins 2
Partners
MRP2NTCP

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 BSEP (Bsep) mediates ATP-dependent transport of monoanionic bile salts in Sf9 cell vesicles; cyclosporin A, rifamycin SV, rifampicin, and glibenclamide cis-inhibit Bsep-mediated bile salt transport; estradiol-17β-glucuronide (E217G) trans-inhibits Bsep only after its Mrp2-dependent secretion into bile canaliculi, establishing that E217G requires Mrp2 to exert its cholestatic effect on Bsep. ATP-dependent vesicle transport assays in Bsep-, Mrp2-, and Bsep/Mrp2-expressing Sf9 cells; rapid filtration technique; canalicular plasma membrane vesicles from rat liver Gastroenterology High 10648470
1998 In endotoxin-treated rats, both mRNA and protein levels of Spgp (BSEP/ABCB11) are decreased, and the normally sharp canalicular localization shifts to a fuzzy subapical pattern, indicating that endotoxin-induced cholestasis involves both reduced BSEP expression and abnormal subcellular localization. RT-PCR, Western blotting of membrane fractions, confocal scanning laser microscopy in endotoxin-treated rats Hepatology Medium 9828229
2001 Knockout of the spgp (Abcb11) gene in mice causes intrahepatic cholestasis with greatly reduced cholic acid secretion (~6% of wild-type); however, total bile salt output is ~30% of wild-type due to secretion of tetra-hydroxylated bile acids and an alternative canalicular transport mechanism, indicating that BSEP is the primary but not sole canalicular bile acid transporter. Abcb11 knockout also increases biliary cholesterol and phospholipid secretion, suggesting intrahepatic bile salts drive biliary lipid secretion. Targeted gene knockout in mice; bile collection and HPLC analysis of bile composition; comparison with wild-type controls Proceedings of the National Academy of Sciences of the United States of America High 11172067
2003 E217G induces endocytic internalization of Bsep from the canalicular membrane in rat liver, dependent on prior Mrp2-mediated secretion of E217G into bile canaliculi; dibutyryl-cAMP (DBcAMP) prevents both cholestasis and Bsep internalization by stimulating insertion of canalicular transporter-containing vesicles. Confocal microscopy and Western blotting of rat liver after E217G administration; hepatocyte couplet fluorescent bile salt accumulation assay; use of TR- (Mrp2-deficient) rats as controls American Journal of Physiology - Gastrointestinal and Liver Physiology High 12702498
2001 Bsep localization in rat liver is dynamically regulated by osmolarity: hypoosmolarity recruits intracellular Bsep vesicles to the canalicular membrane (choleresis), whereas hyperosmolarity causes retrieval of Bsep from the canalicular membrane (cholestasis). Bsep and Mrp2 occupy largely separate intracellular vesicle populations (colocalization in only 15% of intracellular vesicles) during retrieval. Immunohistochemistry, confocal microscopy, and densitometry in perfused rat liver under defined osmotic conditions Hepatology Medium 11230729
2005 The two most common PFIC2 mutations E297G and D482G result in impaired membrane trafficking of BSEP: both mutants predominantly undergo only core glycosylation and are retained in the endoplasmic reticulum; proteasome inhibitor MG132 causes cellular accumulation of the core-glycosylated forms. Despite impaired trafficking, transport function (taurocholate/glycocholate) of the mutants per se is not significantly reduced. Site-directed mutagenesis of human BSEP; expression in HEK293 and MDCK II cells; membrane vesicle transport assays; glycosylation analysis; proteasome inhibition with MG132 Hepatology High 15791618
2005 BSEP can transport the non-bile acid substrate pravastatin in an ATP-dependent manner; human BSEP shows 3.3-fold higher relative uptake of pravastatin vs. taurocholate compared to rat Bsep; pravastatin and taurocholate competitively interact with human BSEP (Km for pravastatin ~124 µM). Several statins inhibit BSEP-mediated taurocholate transport with hydrophilic statins being weaker inhibitors. ATP-dependent uptake assay in membrane vesicles from hBSEP- and rBsep-expressing cells; competitive inhibition studies; species comparison Journal of Pharmacology and Experimental Therapeutics High 15901796
2006 Vectorial transcellular transport of bile salts (basal-to-apical) is reconstituted in LLC-PK1 cells co-expressing NTCP and BSEP; cells expressing only one transporter show no vectorial transport. Substrate specificity reveals BSEP preferentially transports unconjugated bile salts and glycine conjugates over taurine conjugates, with no transport of lithocholate. Double transfection of LLC-PK1 cells with human NTCP+BSEP or rat Ntcp+Bsep; directional flux measurements; substrate clearance calculations American Journal of Physiology - Gastrointestinal and Liver Physiology High 16474011
2006 N-linked glycosylation is required for BSEP protein stability, intracellular trafficking, and transport function: removal of glycans accelerates proteasomal degradation; proteins with fewer than two N-linked glycans fail to reach the apical membrane and are degraded by the proteasome (MG132-sensitive). At least two N-linked glycans (at Asn109, Asn116, Asn122, Asn125) are required for stable apical membrane expression. Site-directed mutagenesis of N-glycosylation sites in rat Bsep-YFP; expression in MDCK II cells; immunoblot, glycosidase cleavage, half-life measurements, proteasome inhibition, taurocholate transport assay American Journal of Physiology - Gastrointestinal and Liver Physiology High 17082223
2007 Clinical phenotype severity (PFIC2 > BRIC2) correlates with the level of BSEP plasma membrane expression: PFIC2 mutant D482G shows the greatest reduction in plasma membrane protein, while BRIC2 mutants (A570T, R1050C) show intermediate reduction. All mutants accumulate in perinuclear aggresome-like structures upon proteasome inhibition, indicating ubiquitin-dependent degradation; treatment with reduced temperature, sodium butyrate, or 4-phenylbutyrate rescues D482G surface expression. Expression of mutant rat Bsep in HEK293 cells; cell surface biotinylation; confocal microscopy; proteasome inhibition with MG132; pharmacological chaperone rescue American Journal of Physiology - Cell Physiology High 17855769
2007 BSEP transport function is impaired in proportion to accelerated protein degradation in disease mutants; BRIC2 mutants (A570T, R1050C) retain ~50% taurocholate transport and longer half-life, while most PFIC2 mutants have near-absent transport. The C-terminal tail (R1057X truncation) is required for transport activity but not for correct targeting to the apical membrane. Mutagenesis of rat Bsep in MDCK II cells; taurocholate transport assay; protein half-life measurement; subcellular distribution by confocal microscopy in polarized monolayers American Journal of Physiology - Gastrointestinal and Liver Physiology High 17947449
2008 Cell-surface-resident BSEP undergoes short-chain ubiquitination (addition of 2–3 ubiquitins, shifting molecular mass from ~170 to ~190 kDa); ubiquitination accelerates BSEP degradation from the cell surface. PFIC2 mutations E297G and D482G enhance BSEP ubiquitination (increasing degradation rate), while 4-phenylbutyrate (4PBA) reduces ubiquitination and prolongs surface BSEP half-life. Ubiquitin modification assay in MDCK II cells and rat canalicular membrane vesicles; biotin-labeling of cell-surface proteins; chimeric ubiquitin-BSEP fusion construct; 4PBA treatment Molecular Pharmacology High 18829893
2009 ABCB11 missense mutations and SNPs impair BSEP at two distinct levels: (1) reduced wild-type pre-mRNA splicing (up to 95% reduction in normal transcript for some mutations; D482G enhances aberrant splicing); (2) ER retention and proteasomal degradation of most missense mutant proteins. Treatment with glycerol or reduced temperature rescues processing of several mutants including E297G. Two assessed mutants (N490D, A570T) show reduced taurocholate transport activity. The SNP A444 shows reduced protein compared to V444. In vitro minigene splicing assay; expression in CHO-K1 cells; immunofluorescence for ER colocalization; glycerol/low-temperature chaperone rescue; membrane vesicle taurocholate transport assay; exogenous splicing factor addition Hepatology High 19101985
2006 Oxidative stress internalizes Bsep from the canalicular membrane and impairs bile salt secretion through a Ca2+-dependent, PKC-mediated mechanism; PKC inhibition (H7, staurosporine, Gö6976) or PKA activation (dibutyryl-cAMP) prevents and reverses Bsep internalization and bile salt secretory failure. F-actin disarrangement accompanies Bsep internalization. Pro-oxidant treatment of isolated rat hepatocyte couplets; fluorescent bile salt analog (CLF) accumulation assay; Bsep immunofluorescence; pharmacological kinase inhibitors/activators; intracellular Ca2+ chelation Toxicological Sciences Medium 16452108
2011 The Src family kinase Fyn (but not Yes or c-Src) mediates hyperosmolarity-induced retrieval of Bsep and Mrp2 from the canalicular membrane; this is driven by NADPH oxidase-derived reactive oxygen species and involves Fyn-dependent phosphorylation of cortactin underneath the canalicular membrane. JNK activation is not involved in transporter retrieval. Perfused rat liver with hyperosmotic buffer; pharmacological Src kinase inhibitors (PP-2, SU6656); p47phox knockout mice; NAC/apocynin as ROS scavengers; Fyn knockdown; cortactin phosphorylation assay; biliary excretion of fluorescent substrates Journal of Biological Chemistry High 22057277
2014 LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane; LKB1 knockout hepatocytes show impaired ABCB11 trafficking and canalicular network formation. In control hepatocytes, ABCB11 traffics through the rab11a–myosin Vb recycling endosomal system and its trafficking is accelerated by taurocholate (via AMPK) and cAMP (via PKA). In LKB1 KO cells, only cAMP/PKA (not taurocholate) restores trafficking. Liver-specific LKB1 knockout mice; collagen sandwich hepatocyte cultures; live cell imaging; FRAP; particle tracking; Western blotting; pharmacological cAMP and AMPK manipulation PLoS One High 24643070
2003 Hepatic overexpression of Abcb11 in transgenic mice increases bile flow and biliary secretion of bile salts, phosphatidylcholine, and cholesterol; it activates FXR/SHP target genes (ileal lipid-binding protein, SHP upregulated; CYP7A1 and ASBT downregulated) by increasing hydrophobic bile salt pool and FXR ligand taurodeoxycholate 4-fold. Abcb11 transgenic mice are resistant to diet-induced hepatic steatosis, establishing ABCB11 as rate-limiting for hepatobiliary bile salt secretion with downstream effects on energy homeostasis. Transthyretin-Abcb11 and BAC-Abcb11 transgenic mice; bile collection; HPLC bile salt analysis; hepatic gene expression by Northern blot/RT-PCR; lithogenic diet challenge Journal of Biological Chemistry High 14570929
2005 In spgp (Abcb11) knockout mice, elevated Mdr1 (P-glycoprotein) expression serves as an alternative bile acid transport pathway; membrane vesicles from Mdr1-overexpressing drug-resistant cells transport bile acids with ~5-fold lower affinity than Spgp, providing the first direct evidence that P-glycoprotein can transport bile acids. Western blotting of ABC transporters in Abcb11 KO mice; ATP-dependent bile acid transport assay in plasma membrane vesicles from Mdr1-overexpressing cell line Biochemistry Medium 16156672
2009 Membrane cholesterol content modulates BSEP transport kinetics: cholesterol loading increases Vmax for bile salt transport in BSEP/Bsep from all three species (human, rat, mouse) without substantially changing Km. The effect is most pronounced in rat Bsep. Cholesterol-loaded vesicles also partially rescue transport activity of disease mutants E297G and R432T. Baculovirus Sf9 expression of human/rat/mouse BSEP; cholesterol loading with cholesterol-cyclodextrin complex; kinetic transport assays with four conjugated bile salts; species-specific inhibitor IC50 determinations Drug Metabolism and Disposition Medium 19520776
2004 LPS downregulates human MRP2 and BSEP protein in liver slices without affecting their mRNA levels, demonstrating that LPS-induced reduction of these transporters in humans occurs via posttranscriptional mechanisms (in contrast to rat, where bsep mRNA is not affected while mrp2 mRNA is reduced). Precision-cut human and rat liver slices treated with LPS; RT-PCR for mRNA; immunofluorescence microscopy for protein; nitrate/nitrite and cytokine measurements American Journal of Physiology - Gastrointestinal and Liver Physiology Medium 15205115
2007 Periportal downregulation of Bsep in obstructive cholestasis (bile duct ligation) is mediated by TNF-α and IL-1β: cytokine inactivation prevents periportal Bsep reduction, while portal inflammation and predominantly periportal IL-1β induction colocalizes with the zone-specific transporter changes. Bile duct ligation in rats; semiquantitative immunofluorescence with zonal analysis; cytokine neutralization with anti-TNF-α and anti-IL-1β antibodies; LPS comparison American Journal of Physiology - Gastrointestinal and Liver Physiology Medium 17916651
2013 Human BSEP (ABCB11) was heterologously expressed and purified from Pichia pastoris; BSEP-GFP localizes to the plasma membrane of P. pastoris; purified BSEP in appropriate detergents binds to ATP-agarose, confirming ATP-binding capability of the isolated protein. Heterologous expression in Pichia pastoris; confocal laser scanning microscopy; detergent screening (>100 detergents); FSEC; ATP-agarose binding assay; purification yielding ~1 mg/100g wet cells PLoS One Medium 23593265
2014 Membrane cholesterol differentially modulates MRP2 and BSEP transport kinetics: for BSEP variants p.V444 and p.A444, cholesterol increases Vmax without changing Km; for BSEP mutants p.E297G and p.R432T, high cholesterol increases transport activity but does not reach wild-type capacity. MRP2 cholesterol effects differ, showing cooperative kinetics for E17βG that shift to Michaelis-Menten at high cholesterol. Baculovirus expression of BSEP variants and mutants in insect cells; cholesterol loading; kinetic transport assays; Hanes-Woolf analysis Molecular Pharmacology Medium 24711118
2005 Novel ABCB11 mutations R432T and E297G (compound heterozygous) found in a BRIC2 patient reduce taurocholate transport to 13% and 20% of reference levels respectively in SF9 cells, while hepatic BSEP expression is preserved (unlike PFIC2 where it is absent), providing direct in vitro evidence for partial loss-of-function causing the benign rather than progressive phenotype. ABCB11 sequencing; taurocholate transport assay in SF9-transfected cells; immunohistochemistry of liver biopsy Journal of Hepatology Medium 16039748
2020 The PFIC2 mutation p.T463I (located in a conserved ABC transporter motif predicted by 3D modelling to impair ATP-binding) reduces taurocholate transport to near-zero despite normal canalicular membrane targeting; ivacaftor treatment increases transport activity of BsepT463I by 1.7-fold, restoring it to 95% of wild-type activity. 3D structure modelling; site-directed mutagenesis; expression in Can10 cells (localization) and MDCK clones co-expressing rat Ntcp (transport); ivacaftor treatment; taurocholate transport assay Liver International Medium 32433800
2012 Abcb11 knockout (C57BL/6J) mice develop cholestasis and show impaired mitochondrial long-chain fatty acid β-oxidation before the onset of cholestasis, with elevated serum free fatty acids, reduced white adipose tissue, increased fatty acid metabolites (phenylpropionylglycine, phenylacetylglycine), and reduced expression of genes for mitochondrial fatty acid oxidation. Abcb11 KO C57BL/6J mice; hepatic lipid metabolism profiling; metabolomics; gene expression analysis; serum biochemistry Journal of Biological Chemistry Medium 22619174
2010 In sandwich-cultured human hepatocytes, IL-6 or IL-1β decrease BSEP mRNA while paradoxically increasing BSEP protein levels, revealing a species-specific discrepancy between mRNA and protein regulation; in rat hepatocytes, TNF-α and IL-1β decrease both Bsep mRNA and protein. Sandwich-cultured human and rat hepatocytes treated with TNF-α, IL-6, IL-1β; Western blot for protein; RT-PCR for mRNA; LPS-treated rat in vivo comparison Journal of Biological Chemistry Medium 20702406
2021 Abcb11-deficient mice spontaneously develop HCC and ICC after 12 months; accumulated bile acids in Abcb11-/- livers are predominantly FXR antagonists/non-agonists, causing downregulation of FXR expression and transcriptional activity; FXR agonist obeticholic acid reduces liver injury and tumor incidence in Abcb11-/- mice, establishing a causal link between ABCB11 deficiency, loss of FXR signaling, and hepatocarcinogenesis. Abcb11-/- mice followed longitudinally; liver histology; RNA-sequencing; bile acid profiling; FXR activity measurement; obeticholic acid treatment rescue experiment Journal of Pathology Medium 34410012

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology 428 10648470
1998 Up-regulation of the multidrug resistance genes, Mrp1 and Mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver. Hepatology (Baltimore, Md.) 302 9828229
2008 Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology 277 18395098
2004 Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. Gastroenterology 245 15300568
2001 Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proceedings of the National Academy of Sciences of the United States of America 240 11172067
2011 The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation. Handbook of experimental pharmacology 210 21103971
2004 Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy. Pharmacogenetics 209 15077010
2010 ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history. Hepatology (Baltimore, Md.) 208 20232290
2008 Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy. Gut 166 18987030
2012 The bile salt export pump (BSEP) in health and disease. Clinics and research in hepatology and gastroenterology 148 22795478
2010 Differences in presentation and progression between severe FIC1 and BSEP deficiencies. Journal of hepatology 142 20447715
2009 Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology (Baltimore, Md.) 140 19101985
2004 LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process. American journal of physiology. Gastrointestinal and liver physiology 131 15205115
2004 BSEP and MDR3 haplotype structure in healthy Caucasians, primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology (Baltimore, Md.) 129 14999697
2005 Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. The Journal of pharmacology and experimental therapeutics 124 15901796
2003 Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. American journal of physiology. Gastrointestinal and liver physiology 112 12702498
2017 An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. Scientific reports 107 28924228
2017 Sequencing of FIC1, BSEP and MDR3 in a large cohort of patients with cholestasis revealed a high number of different genetic variants. Journal of hepatology 102 28733223
2005 Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11. Hepatology (Baltimore, Md.) 94 15791618
2005 Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. Journal of hepatology 94 16039748
2015 Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus. PLoS genetics 92 25625282
2010 Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug metabolism reviews 92 20028269
2005 Bile acid transport in sister of P-glycoprotein (ABCB11) knockout mice. Biochemistry 88 16156672
2001 BSEP: function and role in progressive familial intrahepatic cholestasis. Seminars in liver disease 88 11745042
2006 Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11). Drug metabolism and disposition: the biological fate of chemicals 80 16763017
2003 Semi quantitative expression analysis of MDR3, FIC1, BSEP, OATP-A, OATP-C,OATP-D, OATP-E and NTCP gene transcripts in 1st and 3rd trimester human placenta. Placenta 80 12495658
2003 Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. The Journal of biological chemistry 80 14570929
2007 Regulation of hepatic bile acid transporters Ntcp and Bsep expression. Biochemical pharmacology 74 17897632
2009 Effect of membrane cholesterol on BSEP/Bsep activity: species specificity studies for substrates and inhibitors. Drug metabolism and disposition: the biological fate of chemicals 73 19520776
2007 Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. American journal of physiology. Cell physiology 73 17855769
2002 FIC1 and BSEP defects in Taiwanese patients with chronic intrahepatic cholestasis with low gamma-glutamyltranspeptidase levels. The Journal of pediatrics 72 11815775
2012 Abcb11 deficiency induces cholestasis coupled to impaired β-fatty acid oxidation in mice. The Journal of biological chemistry 71 22619174
2001 Regulation of the dynamic localization of the rat Bsep gene-encoded bile salt export pump by anisoosmolarity. Hepatology (Baltimore, Md.) 67 11230729
2013 Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations. Molecular aspects of medicine 63 23685087
2006 Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep. American journal of physiology. Gastrointestinal and liver physiology 63 16474011
2016 Metabolic preconditioning protects BSEP/ABCB11-/- mice against cholestatic liver injury. Journal of hepatology 59 27593105
2010 Regulation of MRP2/ABCC2 and BSEP/ABCB11 expression in sandwich cultured human and rat hepatocytes exposed to inflammatory cytokines TNF-{alpha}, IL-6, and IL-1{beta}. The Journal of biological chemistry 57 20702406
2008 Cloning and molecular characterization of apical efflux transporters (ABCB1, ABCB11 and ABCC2) in rainbow trout (Oncorhynchus mykiss) hepatocytes. Aquatic toxicology (Amsterdam, Netherlands) 56 19008001
2007 Obstructive cholestasis induces TNF-alpha- and IL-1 -mediated periportal downregulation of Bsep and zonal regulation of Ntcp, Oatp1a4, and Oatp1b2. American journal of physiology. Gastrointestinal and liver physiology 55 17916651
2015 Geniposidic acid protected against ANIT-induced hepatotoxity and acute intrahepatic cholestasis, due to Fxr-mediated regulation of Bsep and Mrp2. Journal of ethnopharmacology 53 26723467
2006 Oxidative stress induces internalization of the bile salt export pump, Bsep, and bile salt secretory failure in isolated rat hepatocyte couplets: a role for protein kinase C and prevention by protein kinase A. Toxicological sciences : an official journal of the Society of Toxicology 53 16452108
2012 ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 52 23022423
2015 Autoimmune BSEP disease: disease recurrence after liver transplantation for progressive familial intrahepatic cholestasis. Clinical reviews in allergy & immunology 49 25342496
2010 Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability. Pharmacogenetics and genomics 49 20010382
2017 Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing. Journal of gastroenterology 48 29238877
2008 Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11). Molecular pharmacology 47 18829893
2006 Effect of culture conditions on the expression and function of Bsep, Mrp2, and Mdr1a/b in sandwich-cultured rat hepatocytes. Biochemical pharmacology 47 16542640
2002 Asynchronous expression and colocalization of Bsep and Mrp2 during development of rat liver. American journal of physiology. Gastrointestinal and liver physiology 47 11842005
2018 Dysregulation of BSEP and MRP2 May Play an Important Role in Isoniazid-Induced Liver Injury via the SIRT1/FXR Pathway in Rats and HepG2 Cells. Biological & pharmaceutical bulletin 46 30068870
2015 The inhibition of hepatic bile acids transporters Ntcp and Bsep is involved in the pathogenesis of isoniazid/rifampicin-induced hepatotoxicity. Toxicology mechanisms and methods 46 25886055
2007 Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells. American journal of physiology. Gastrointestinal and liver physiology 46 17947449
2011 A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease. Clinical science (London, England : 1979) 43 20883210
2015 Recent advances in the exploration of the bile salt export pump (BSEP/ABCB11) function. Expert opinion on therapeutic targets 42 26573700
2006 Two N-linked glycans are required to maintain the transport activity of the bile salt export pump (ABCB11) in MDCK II cells. American journal of physiology. Gastrointestinal and liver physiology 42 17082223
2022 Alisol B 23-acetate adjusts bile acid metabolisim via hepatic FXR-BSEP signaling activation to alleviate atherosclerosis. Phytomedicine : international journal of phytotherapy and phytopharmacology 40 35523117
2016 Disruption of BSEP Function in HepaRG Cells Alters Bile Acid Disposition and Is a Susceptive Factor to Drug-Induced Cholestatic Injury. Molecular pharmaceutics 40 26910619
2014 LKB1/AMPK and PKA control ABCB11 trafficking and polarization in hepatocytes. PloS one 40 24643070
2011 BSEP inhibition: in vitro screens to assess cholestatic potential of drugs. Toxicology in vitro : an international journal published in association with BIBRA 40 22120137
2005 Experimental LPS-induced cholestasis alters subcellular distribution and affects colocalization of Mrp2 and Bsep proteins: a quantitative colocalization study. Microscopy research and technique 40 16037978
2003 Differential developmental regulation of rat liver canalicular membrane transporters Bsep and Mrp2. Pediatric research 40 12538788
2016 BSEP and MDR3: Useful Immunohistochemical Markers to Discriminate Hepatocellular Carcinomas From Intrahepatic Cholangiocarcinomas and Hepatoid Carcinomas. The American journal of surgical pathology 36 26735860
2023 Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions. Cell genomics 35 37601975
2020 Functional rescue of an ABCB11 mutant by ivacaftor: A new targeted pharmacotherapy approach in bile salt export pump deficiency. Liver international : official journal of the International Association for the Study of the Liver 35 32433800
2009 Recent insights into the function and regulation of the bile salt export pump (ABCB11). Current opinion in lipidology 35 19684528
2020 Review article: liver disease in adults with variants in the cholestasis-related genes ABCB11, ABCB4 and ATP8B1. Alimentary pharmacology & therapeutics 34 33070363
2010 Recurrent low gamma-glutamyl transpeptidase cholestasis following liver transplantation for bile salt export pump (BSEP) disease (posttransplant recurrent BSEP disease). Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 34 20583290
2014 Hepatic bile acid metabolism and expression of cytochrome P450 and related enzymes are altered in Bsep (-/-) mice. Molecular and cellular biochemistry 33 24399466
2009 Common variants of ABCB4 and ABCB11 and plasma lipid levels: a study in sib pairs with gallstones, and controls. Lipids 33 19408031
2002 Appearance of atypical 3 alpha,6 beta,7 beta,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid in spgp knockout mice. Journal of lipid research 33 12562825
2019 Emodin Rescues Intrahepatic Cholestasis via Stimulating FXR/BSEP Pathway in Promoting the Canalicular Export of Accumulated Bile. Frontiers in pharmacology 32 31191298
2019 Tanshinone IIA prevents rifampicin-induced liver injury by regulating BSEP/NTCP expression via epigenetic activation of NRF2. Liver international : official journal of the International Association for the Study of the Liver 32 31571363
2002 Ursodeoxycholic acid (UDCA) prevents DCA effects on male mouse liver via up-regulation of CYP [correction of CXP] and preservation of BSEP activities. Hepatology (Baltimore, Md.) 32 12143038
2021 Regulatory mechanisms of the bile salt export pump (BSEP/ABCB11) and its role in related diseases. Clinics and research in hepatology and gastroenterology 31 33581308
2016 Dioscin protects against ANIT-induced cholestasis via regulating Oatps, Mrp2 and Bsep expression in rats. Toxicology and applied pharmacology 30 27317372
2003 Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharmaceutical research 30 12739759
2014 Paediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations. Journal of hepatology 29 25016225
2002 Effect of Ursodeoxycholic Acid on the Expression of the Hepatocellular Bile Acid Transporters (Ntcp and bsep) in Rats With Estrogen-Induced Cholestasis. Journal of pediatric gastroenterology and nutrition 29 12187295
2014 Differential effects of membrane cholesterol content on the transport activity of multidrug resistance-associated protein 2 (ABCC2) and of the bile salt export pump (ABCB11). Molecular pharmacology 28 24711118
2013 Detergent screening and purification of the human liver ABC transporters BSEP (ABCB11) and MDR3 (ABCB4) expressed in the yeast Pichia pastoris. PloS one 28 23593265
2015 In vitro model systems to investigate bile salt export pump (BSEP) activity and drug interactions: A review. Chemico-biological interactions 27 26683212
2012 Differential effect of troglitazone on the human bile acid transporters, MRP2 and BSEP, in the PXB hepatic chimeric mouse. Toxicologic pathology 26 22673116
2009 ABCB11 gene mutations in Chinese children with progressive intrahepatic cholestasis and low gamma glutamyltransferase. Liver international : official journal of the International Association for the Study of the Liver 26 19845854
2020 Absence of Bsep/Abcb11 attenuates MCD diet-induced hepatic steatosis but aggravates inflammation in mice. Liver international : official journal of the International Association for the Study of the Liver 25 32141703
2014 Variations of ABCB4 and ABCB11 genes are associated with primary intrahepatic stones. Molecular medicine reports 25 25323205
2005 Steatohepatitis develops rapidly in transgenic mice overexpressing Abcb11 and fed a methionine-choline-deficient diet. American journal of physiology. Gastrointestinal and liver physiology 25 15650132
2008 Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins. Biopharmaceutics & drug disposition 24 18985798
2005 Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of cAMP. Biochemical pharmacology 24 15763547
2021 Disordered farnesoid X receptor signaling is associated with liver carcinogenesis in Abcb11-deficient mice. The Journal of pathology 23 34410012
2011 The Src family kinase Fyn mediates hyperosmolarity-induced Mrp2 and Bsep retrieval from canalicular membrane. The Journal of biological chemistry 23 22057277
2010 The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C. Journal of viral hepatitis 23 20723035
2021 The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies. International journal of molecular sciences 22 33466755
2000 Bile salt excretion in skate liver is mediated by a functional analog of Bsep/Spgp, the bile salt export pump. American journal of physiology. Gastrointestinal and liver physiology 22 10644562
2015 Yinzhihuang attenuates ANIT-induced intrahepatic cholestasis in rats through upregulation of Mrp2 and Bsep expressions. Pediatric research 21 26646631
2018 Diagnosis of cirrhosis in patients with chronic hepatitis C genotype 4: Role of ABCB11 genotype polymorphism and plasma bile acid levels. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 20 29755014
2017 Structure based classification for bile salt export pump (BSEP) inhibitors using comparative structural modeling of human BSEP. Journal of computer-aided molecular design 20 28527154
2016 Up-regulation of BSEP and MRP2 by Calculus Bovis administration in 17α-ethynylestradiol-induced cholestasis: Involvement of PI3K/Akt signaling pathway. Journal of ethnopharmacology 20 27237619
2012 NR1H4 analysis in patients with progressive familial intrahepatic cholestasis, drug-induced cholestasis or intrahepatic cholestasis of pregnancy unrelated to ATP8B1, ABCB11 and ABCB4 mutations. Clinics and research in hepatology and gastroenterology 20 23142591
2019 The Role of the Sodium-taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) in Related Liver Disease. Current drug metabolism 19 31258056
2017 The role of Ntcp, Oatp2, Bsep and Mrp2 in liver injury induced by Dioscorea bulbifera L. and Diosbulbin B in mice. Environmental toxicology and pharmacology 19 28262508
2011 Hepatic overexpression of abcb11 promotes hypercholesterolemia and obesity in mice. Gastroenterology 19 21726512

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