{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNotably, none of the provided abstracts address VSTM5. Instead, the studies focus on the sodium taurocholate cotransporting polypeptide (NTCP; gene SLC10A1) and its multifaceted role in hepatocyte function. NTCP is shown to be critical for the hepatic uptake of conjugated bile acids and, importantly, acts as a receptor mediating the entry of hepatitis B and D viruses into susceptible cells. Its proper function ensures bile acid homeostasis and influences viral infectivity, as illustrated by its species‐specific domains that determine viral entry competence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA second major theme among these abstracts is the regulation of NTCP expression and activity at both the transcriptional and post‐translational levels. Multiple studies detail how nuclear receptors and hepatocyte‐enriched transcription factors (for example, HNF-4α, HNF-1α, RXRα/RARα, and C/EBPβ) govern NTCP gene expression in a species-specific manner. In addition, NTCP function is modified by cellular signals such as bile acid accumulation, cytokine exposure, and chemical challenges—including exposure to perfluorinated compounds and drugs such as isoniazid and rifampicin—that can down-regulate its expression and activity. These findings illustrate the complex interplay between metabolic, chemical, and inflammatory signals in modulating NTCP-mediated bile acid uptake."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA third important aspect discussed in these studies is the relevance of NTCP in disease contexts and physiological adaptations. In models of cholestasis, liver regeneration after partial hepatectomy, and certain drug-induced liver injuries, altered NTCP expression contributes to the compensatory adjustments of bile acid synthesis, detoxification, and transporter activity. Moreover, genetic deletion or pharmacological inhibition of NTCP not only affects bile acid clearance but may also modulate energy homeostasis and susceptibility to obesity and hepatic steatosis. Collectively, these observations underscore NTCP’s pivotal role within the enterohepatic circulation and its potential as a therapeutic target. It is important to bear in mind that while these abstracts provide a wealth of insight into NTCP function and regulation, they do not offer any information on VSTM5, suggesting that the role of VSTM5 remains to be defined in these contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Henk Wolters, Baukje M Elzinga, Julius F W Baller, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00319.2004"}], "href": "https://doi.org/10.1152/ajpgi.00319.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16002565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16002565"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tohru Saeki, Yuki Munetaka, Kazumitsu Ueda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of Ala substitution for conserved Cys residues in mouse ileal and hepatic Na+-dependent bile acid transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Biotechnol Biochem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1271/bbb.70037"}], "href": "https://doi.org/10.1271/bbb.70037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17690477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17690477"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xingguo Cheng, David Buckley, Curtis D Klaassen "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of hepatic bile acid transporters Ntcp and Bsep expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcp.2007.08.014"}], "href": "https://doi.org/10.1016/j.bcp.2007.08.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17897632"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17897632"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xingguo Cheng, Curtis D Klaassen "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of PPAR-alpha in perfluorooctanoic acid- and perfluorodecanoic acid-induced downregulation of Oatp uptake transporters in mouse livers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/toxsci/kfn161"}], "href": "https://doi.org/10.1093/toxsci/kfn161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18703564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18703564"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Satoki Imai, Ryota Kikuchi, Hiroyuki Kusuhara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of DNA methylation and histone modification profiles of liver-specific transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.108.052589"}], "href": "https://doi.org/10.1124/mol.108.052589"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19047482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19047482"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Iván L Csanaky, Lauren M Aleksunes, Yuji Tanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of hepatic transporters in prevention of bile acid toxicity after partial hepatectomy in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.90728.2008"}], "href": "https://doi.org/10.1152/ajpgi.90728.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19497955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19497955"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nathan J Cherrington, Teresa E Estrada, Harrison A Frisk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00317.2012"}], "href": "https://doi.org/10.1152/ajpgi.00317.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23125159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23125159"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Huan Yan, Bo Peng, Wenhui He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular determinants of hepatitis B and D virus entry restriction in mouse sodium taurocholate cotransporting polypeptide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.03540-12"}], "href": "https://doi.org/10.1128/JVI.03540-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23678176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23678176"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Davor Slijepcevic, Christina Kaufman, Catharina G K Wichers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired uptake of conjugated bile acids and hepatitis b virus pres1-binding in na(+) -taurocholate cotransporting polypeptide knockout mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.27694"}], "href": "https://doi.org/10.1002/hep.27694"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25641256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25641256"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Annika Sommerfeld, Patrick G K Mayer, Miriam Cantore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of plasma membrane localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by hyperosmolarity and tauroursodeoxycholate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.666883"}], "href": "https://doi.org/10.1074/jbc.M115.666883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26306036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26306036"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Davor Slijepcevic, Reinout L P Roscam Abbing, Takeshi Katafuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.29251"}], "href": "https://doi.org/10.1002/hep.29251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28498614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28498614"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Fengfeng Mao, Teng Liu, Xinfeng Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.007179"}], "href": "https://doi.org/10.1074/jbc.RA118.007179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31201272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31201272"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Joanne M Donkers, Sander Kooijman, Davor Slijepcevic, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Sodium"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "/taurocholate cotransporting polypeptide as target therapy for liver fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gutjnl-2020-323345"}], "href": "https://doi.org/10.1136/gutjnl-2020-323345"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34266968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34266968"}]}]}]}