Ontology type: schema:ScholarlyArticle
2021-10-23
AUTHORSTomas Smutny, Veronika Bernhauerova, Lucie Smutna, Jurjen Duintjer Tebbens, Petr Pavek
ABSTRACTThe pregnane X receptor (PXR) is a ligand-activated nuclear receptor controlling hepatocyte expression of numerous genes. Although expression changes in xenobiotic-metabolizing, lipogenic, gluconeogenic and bile acid synthetic genes have been described after PXR activation, the temporal dynamics of their expression is largely unknown. Recently, 3D spheroids of primary human hepatocytes (PHHs) have been characterized as the most phenotypically relevant hepatocyte model. We used 3D PHHs to assess time-dependent expression profiles of 12 prototypic PXR-controlled genes in the time course of 168 h of rifampicin treatment (1 or 10 µM). We observed a similar bell-shaped time-induction pattern for xenobiotic-handling genes (CYP3A4, CYP2C9, CYP2B6, and MDR1). However, we observed either biphasic profiles for genes involved in endogenous metabolism (FASN, GLUT2, G6PC, PCK1, and CYP7A1), a decrease for SHP or oscillation for PDK4 and PXR. The rifampicin concentration determined the expression profiles for some genes. Moreover, we calculated half-lives of CYP3A4 and CYP2C9 mRNA under induced or basal conditions and we used a mathematical model to describe PXR-mediated regulation of CYP3A4 expression employing 3D PHHs. The study shows the importance of long-term time-expression profiling of PXR target genes in phenotypically stable 3D PHHs and provides insight into PXR function in liver beyond our knowledge from conventional 2D in vitro models. More... »
PAGES195-210
http://scigraph.springernature.com/pub.10.1007/s00204-021-03177-y
DOIhttp://dx.doi.org/10.1007/s00204-021-03177-y
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1142121036
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/34689256
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1115",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Pharmacology and Pharmaceutical Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cytochrome P-450 CYP3A",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Hepatocytes",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Pregnane X Receptor",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Receptors, Cytoplasmic and Nuclear",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Receptors, Steroid",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic",
"id": "http://www.grid.ac/institutes/grid.4491.8",
"name": [
"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic"
],
"type": "Organization"
},
"familyName": "Smutny",
"givenName": "Tomas",
"id": "sg:person.01172731354.64",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01172731354.64"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic",
"id": "http://www.grid.ac/institutes/grid.4491.8",
"name": [
"Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic"
],
"type": "Organization"
},
"familyName": "Bernhauerova",
"givenName": "Veronika",
"id": "sg:person.01313336663.18",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313336663.18"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic",
"id": "http://www.grid.ac/institutes/grid.4491.8",
"name": [
"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic"
],
"type": "Organization"
},
"familyName": "Smutna",
"givenName": "Lucie",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic",
"id": "http://www.grid.ac/institutes/grid.4491.8",
"name": [
"Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic"
],
"type": "Organization"
},
"familyName": "Tebbens",
"givenName": "Jurjen Duintjer",
"id": "sg:person.0613272602.31",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0613272602.31"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic",
"id": "http://www.grid.ac/institutes/grid.4491.8",
"name": [
"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic"
],
"type": "Organization"
},
"familyName": "Pavek",
"givenName": "Petr",
"id": "sg:person.01153106200.96",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01153106200.96"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.1007/s00204-020-02916-x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1132444915",
"https://doi.org/10.1007/s00204-020-02916-x"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.21136/am.2019.0284-18",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1112911562",
"https://doi.org/10.21136/am.2019.0284-18"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s10565-011-9208-4",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011794647",
"https://doi.org/10.1007/s10565-011-9208-4"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/s41467-017-00780-5",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1091963204",
"https://doi.org/10.1038/s41467-017-00780-5"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.2165/00003088-197803020-00002",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007109951",
"https://doi.org/10.2165/00003088-197803020-00002"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/clpt.2013.48",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021656193",
"https://doi.org/10.1038/clpt.2013.48"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/s41598-018-32722-6",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1107094100",
"https://doi.org/10.1038/s41598-018-32722-6"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/clpt.2012.68",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1004025588",
"https://doi.org/10.1038/clpt.2012.68"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ncomms2799",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014167900",
"https://doi.org/10.1038/ncomms2799"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s11538-010-9508-5",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1017925330",
"https://doi.org/10.1007/s11538-010-9508-5"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s00204-013-1078-5",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1044699368",
"https://doi.org/10.1007/s00204-013-1078-5"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/srep25187",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028498125",
"https://doi.org/10.1038/srep25187"
],
"type": "CreativeWork"
}
],
"datePublished": "2021-10-23",
"datePublishedReg": "2021-10-23",
"description": "The pregnane X receptor (PXR) is a ligand-activated nuclear receptor controlling hepatocyte expression of numerous genes. Although expression changes in xenobiotic-metabolizing, lipogenic, gluconeogenic and bile acid synthetic genes have been described after PXR activation, the temporal dynamics of their expression is largely unknown. Recently, 3D spheroids of primary human hepatocytes (PHHs) have been characterized as the most phenotypically relevant hepatocyte model. We used 3D PHHs to assess time-dependent expression profiles of 12 prototypic PXR-controlled genes in the time course of 168\u00a0h of rifampicin treatment (1 or 10\u00a0\u00b5M). We observed a similar bell-shaped time-induction pattern for xenobiotic-handling genes (CYP3A4, CYP2C9, CYP2B6, and MDR1). However, we observed either biphasic profiles for genes involved in endogenous metabolism (FASN, GLUT2, G6PC, PCK1, and CYP7A1), a decrease for SHP or oscillation for PDK4 and PXR. The rifampicin concentration determined the expression profiles for some genes. Moreover, we calculated half-lives of CYP3A4 and CYP2C9 mRNA under induced or basal conditions and we used a mathematical model to describe PXR-mediated regulation of CYP3A4 expression employing 3D PHHs. The study shows the importance of long-term time-expression profiling of PXR target genes in phenotypically stable 3D PHHs and provides insight into PXR function in liver beyond our knowledge from conventional 2D in vitro models.",
"genre": "article",
"id": "sg:pub.10.1007/s00204-021-03177-y",
"inLanguage": "en",
"isAccessibleForFree": false,
"isFundedItemOf": [
{
"id": "sg:grant.8864553",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1019669",
"issn": [
"0340-5761",
"1432-0738"
],
"name": "Archives of Toxicology",
"publisher": "Springer Nature",
"type": "Periodical"
},
{
"issueNumber": "1",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "96"
}
],
"keywords": [
"pregnane X receptor",
"primary human hepatocytes",
"expression profiles",
"time-dependent expression profiles",
"numerous genes",
"expression dynamics",
"PXR target genes",
"target genes",
"synthetic gene",
"expression changes",
"PXR function",
"genes",
"nuclear receptors",
"X receptor",
"PXR activation",
"endogenous metabolism",
"expression",
"CYP2C9 mRNA",
"human hepatocytes",
"temporal dynamics",
"hepatocyte model",
"CYP3A4 expression",
"receptors",
"PDK4",
"basal conditions",
"mRNA",
"profiling",
"regulation",
"rifampicin treatment",
"hepatocyte spheroids",
"metabolism",
"SHP",
"spheroids",
"activation",
"hepatocyte expression",
"rifampicin concentrations",
"hepatocytes",
"dynamics",
"time course",
"insights",
"profile",
"patterns",
"function",
"biphasic profile",
"importance",
"changes",
"liver",
"concentration",
"knowledge",
"conditions",
"decrease",
"study",
"CYP3A4",
"model",
"human hepatocyte spheroids",
"treatment",
"conventional 2D",
"mathematical model",
"oscillations",
"course",
"primary human hepatocyte spheroids"
],
"name": "Expression dynamics of pregnane X receptor-controlled genes in 3D primary human hepatocyte spheroids",
"pagination": "195-210",
"productId": [
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1142121036"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1007/s00204-021-03177-y"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"34689256"
]
}
],
"sameAs": [
"https://doi.org/10.1007/s00204-021-03177-y",
"https://app.dimensions.ai/details/publication/pub.1142121036"
],
"sdDataset": "articles",
"sdDatePublished": "2022-05-20T07:38",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-springernature-scigraph/baseset/20220519/entities/gbq_results/article/article_886.jsonl",
"type": "ScholarlyArticle",
"url": "https://doi.org/10.1007/s00204-021-03177-y"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00204-021-03177-y'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00204-021-03177-y'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00204-021-03177-y'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00204-021-03177-y'
This table displays all metadata directly associated to this object as RDF triples.
226 TRIPLES
22 PREDICATES
105 URIs
85 LITERALS
13 BLANK NODES