المؤلفون: Anna, Baghdasaryan, Peter, Chiba, Michael, Trauner

المصدر: Molecular Aspects of Medicine

مصطلحات موضوعية: PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1 alpha, FXR, farnesoid X receptor (NR1H4), HNF4α, hepatocyte nuclear factor 4 alpha, CARM1, co-activator-associated arginine methyltransferase 1, OATP, organic anion transporting polypeptide, VDR (NR1I1), vitamin D receptor, Review, BCRP (ABCG2), breast cancer resistance protein, NDRG2, NMYC downstrean-regulated gene 2, MRP4 (ABCC4), multidrug resistance-associated protein 4, SRC2, steroid receptor co-activator 2, GGT, gamma-glutamyl transpeptidase, MDR1 (ABCB1), multidrug resistance protein 1, Nuclear receptors, GRE, glucocorticoid response element, CtBP, C-terminal binding protein, GCA, glycocholic acid, TβMCA, β-tauromuricholic acid, TNF-α, tumor necrosis factor alpha, ATB-binding cassette transporters, FGF19/FGF15, fibroblast growth factor 19/15, MARE, MAF recognition element, ATP Binding Cassette Transporter, Subfamily B, Member 11, TCDCA, taurochenodeoxycholic acid, CA, cholic acid, Cholestasis, ASBT (SLC10A2), apical sodium-dependent bile acid transporter, Symporters, AE2 (SLC4A2), anion exchanger 2, ABC, ATP-binding cassette, FXRE, FXR response element, cAMP, cyclic adenosine monophosphate, DILI, drug-induced liver injury, IL-6, interleukin 6, PL, phospholipid, TGR5, G protein coupled bile acid receptor, OCA, obeticholic acid, OSTα/OSTβ (SLC51A/SLC51B), organic solute transporter alpha/beta, LRH1 (NR5A2), liver receptor homologue 1, JNK, c-Jun N-terminal kinase, NRF2, nuclear factor erythroid 2-related factor 2, LPS, lipopolysaccharide, BRIC2, benign recurrent intrahepatic cholestasis type 2, LXR (NR1H3), liver X receptor, Transcriptional Activation, PFIC2, progressive familial intrahepatic cholestasis type 2, PXR (NR1I2), pregnane X receptor, TCA, taurocholic acid, RXRα (NR2B1), retinoid X receptor, Organic Anion Transporters, Sodium-Dependent, CCl4, carbone tetrachloride, UDCA, ursodeoxycholic acid, Bile Acids and Salts, CDCA, chenodeoxycholic acid, STAT-5, signal transducer and activator of transcription 5, LCA, litocholic acid, ALT, alanine aminotransferase, CBDL, common bile duct ligation, IR-1, inverse repeat 1, TUDCA, tauroursodeoxycholic acid, Humans, ICP, intrahepatic cholestasis of pregnancy, GR (NR3C1), glucocorticoid receptor, MRP2 (ABCC2), multidrug resistance-associated protein 2, TαMCA, α-tauromuricholic acid, TPN, total parenteral nutrition, ALP, alkaline phosphatase, IL-1β, interleukin-1 beta, SREBP1, sterol regulatory element-binding protein 1, Membrane Transport Proteins, Biological Transport, BSEP (ABCB11), bile salt export pump, MAF, musculo-aponeurotic fibrosacroma, ASCOM, activating signal cointegrator-2-containing complex, HNF1α, hepatocyte nuclear factor 1 alpha, MCL-1, myeloid cell leukemia factor 1, NTCP (SLC10A1), Na+-taurocholate cotransporting polypeptide solute carrier family 10 member 1, VPAC-1, vasoactive intestinal polypeptide activated receptor, AMPK, AMP-activated protein kinase, MRP3 (ABCC3), multidrug resistance-associated protein 3, NF-κB, nuclear factor kappa-B, PSC, primary sclerosing cholangitis, Gene Expression Regulation, DCA, deoxycholic acid, BS, bile salt, MDR2 (ABCB4), multidrug resistance protein 2, PPARα (NR1C1), peroxisome proliferator-activated receptor alpha, SHP (NR0B2), short heterodimer partner, RARα (NR1B1), retinoic acid receptor, ATP-Binding Cassette Transporters, PBC, primary biliary cirrhosis, PPARγ (NR1C3), peroxisome proliferator-activated receptor gamma

الوصف: Hepatobiliary bile salt (BS) transporters are critical determinants of BS homeostasis controlling intracellular concentrations of BSs and their enterohepatic circulation. Genetic or acquired dysfunction of specific transport systems causes intrahepatic and systemic retention of potentially cytotoxic BSs, which, in high concentrations, may disturb integrity of cell membranes and subcellular organelles resulting in cell death, inflammation and fibrosis. Transcriptional regulation of canalicular BS efflux through bile salt export pump (BSEP), basolateral elimination through organic solute transporters alpha and beta (OSTα/OSTβ) as well as inhibition of hepatocellular BS uptake through basolateral Na(+)-taurocholate cotransporting polypeptide (NTCP) represent critical steps in protection from hepatocellular BS overload and can be targeted therapeutically. In this article, we review the potential clinical implications of the major BS transporters BSEP, OSTα/OSTβ and NTCP in the pathogenesis of hereditary and acquired cholestatic syndromes, provide an overview on transcriptional control of these transporters by the key regulatory nuclear receptors and discuss the potential therapeutic role of novel transcriptional activators of BS transporters in cholestasis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::02c2316b6e5fe1c1e107f32e273f6aebTest
https://pubmed.ncbi.nlm.nih.gov/24333169Test

المؤلفون: Emina Halilbasic, Thierry Claudel, Michael Trauner

المصدر: Journal of Hepatology
Journal of Hepatology; Vol 58

مصطلحات موضوعية: ABCG5/8, cholesterol efflux pump, ATP-binding cassette, subfamily G, member 5/8, NTCP (SLC10A1), sodium/taurocholate cotransporting polypeptide, solute carrier family 10, member 1, TGR5, G protein-coupled bile acid receptor, Receptors, Cytoplasmic and Nuclear, Review, Mdr2/MDR3 (ABCB4), multidrug resistance protein 2 (rodents)/3 (human), MRP4 (ABCC4), multidrug resistance-associated protein 4, ATP-binding cassette, subfamily C, member 4, Intestinal absorption, 0302 clinical medicine, RXRα (NR2B1), retinoid X receptor alpha, PFIC, progressive familial intrahepatic cholestasis, FXR (NR1H4), farnesoid X receptor/bile acid receptor, AE2, anion exchanger 2, LCA, lithocholic acid, VDR (NR1I1), vitamin D receptor. Please note that for the convenience of better readability and clarity, abbreviations for transporters and nuclear receptors were capitalized throughout this article when symbols were identical for human and rodents, 0303 health sciences, OATP1B3 (SLCO1B3, OATP8, SLC21A8), solute carrier organic anion transporter family, member 1B3, Cholestasis, Membrane Glycoproteins, BCRP (ABCG2), breast cancer resistance protein, ATP-binding cassette, subfamily G, member 2, BRIC, benign recurrent intrahepatic cholestasis, Bile acid, Liver Diseases, Progressive familial intrahepatic cholestasis, NR, nuclear receptor, FGF15/19, fibroblast growth factor 15/19, G protein-coupled bile acid receptor, GLP-1, glucagon like peptide 1, MRP3 (ABCC3), multidrug resistance-associated protein 3, ATP-binding cassette, subfamily C, member 3, Ursodeoxycholic acid, 3. Good health, RARα (NR1B1), retinoic acid receptor alpha, TNFα, tumor necrosis factor α, Biochemistry, Liver, FGF15/19, BA, bile acid, CAR (NR1I3), constitutive androstane receptor, 030211 gastroenterology & hepatology, medicine.drug, NAFLD, non-alcoholic fatty liver disease, PXR (NR1I2), pregnane X receptor, medicine.drug_class, PH, partial hepatectomy, IL6, interleukin 6, NASH, non-alcoholic steatohepatitis, 6-ECDCA, 6-ethylchenodeoxycholic acid, LXRα (NR1H3), liver X receptor alpha, Biology, MRP2 (ABCC2), multidrug resistance-associated protein 2, ATP-binding cassette, subfamily C, member 2, UDCA, ursodeoxycholic acid, Bile Acids and Salts, 03 medical and health sciences, medicine, Animals, Humans, ICP, intrahepatic cholestasis of pregnancy, MDR1 (ABCB1), p-glycoprotein, ATP-binding cassette, subfamily B, member 1, 030304 developmental biology, GR (NR3C1), glucocorticoid receptor, TPN, total parenteral nutrition, Hepatology, Liver receptor homolog-1, BSEP (ABCB11), bile salt export pump, HNF1α, hepatocyte nuclear factor 1 alpha, medicine.disease, LRH-1 (NR5A2), liver receptor homolog-1, Bile acids, OSTαβ, organic solute transporter alpha/beta, Liver Regeneration, EGFR, epidermal growth factor receptor, Bile acids, Cholestasis, Fatty liver disease, Gallstones, Liver regeneration, Liver cancer, norUDCA, norursodeoxycholic acid, PSC, primary sclerosing cholangitis, OATP1B1 (SLCO1B1, OATP2, OATP-C, SLC21A6), solute carrier organic anion transporter family, member 1B1, SRC2, p160 steroid receptor coactivator, PPARα (NR1C1), peroxisome proliferator-activated receptor alpha, AMPK, AMP activated protein kinase, SHP (NR0B2), short heterodimer partner, OATP1A2 (SLCO1A2, OATP1, OATP-A, SLC21A3), solute carrier organic anion transporter family, member 1A2, PBC, primary biliary cirrhosis, IBABP (FABP6, ILBP), intestinal bile acid-binding protein, fatty acid-binding protein 6, Carrier Proteins, HCC, hepatocellular carcinoma, HNF4α (NR2A1), hepatocyte nuclear factor 4 alpha, PPARγ (NR1C3), peroxisome proliferator-activated receptor gamma

الوصف: Summary Bile acid (BA) transporters are critical for maintenance of the enterohepatic BA circulation where BAs exert their multiple physiological functions including stimulation of bile flow, intestinal absorption of lipophilic nutrients, solubilization and excretion of cholesterol, as well as antimicrobial and metabolic effects. Tight regulation of BA transporters via nuclear receptors is necessary to maintain proper BA homeostasis. Hereditary and acquired defects of BA transporters are involved in the pathogenesis of several hepatobiliary disorders including cholestasis, gallstones, fatty liver disease and liver cancer, but also play a role in intestinal and metabolic disorders beyond the liver. Thus, pharmacological modification of BA transporters and their regulatory nuclear receptors opens novel treatment strategies for a wide range of disorders.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5e9e0dc14c7aa1eedb7912aef1d18f5Test
https://pubmed.ncbi.nlm.nih.gov/22885388Test