{"id":"https://openalex.org/W3097684663","doi":"https://doi.org/10.1182/blood-2020-143330","title":"Loss of FXR Signaling Promotes Chronic Liver Injury in Sickle Cell Disease","display_name":"Loss of FXR Signaling Promotes Chronic Liver Injury in Sickle Cell Disease","publication_year":2020,"publication_date":"2020-11-04","ids":{"openalex":"https://openalex.org/W3097684663","doi":"https://doi.org/10.1182/blood-2020-143330","mag":"3097684663"},"language":"en","primary_location":{"id":"doi:10.1182/blood-2020-143330","doi":"https://doi.org/10.1182/blood-2020-143330","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2020-143330","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5019787609","display_name":"Ravi Vats","orcid":"https://orcid.org/0009-0009-9987-8828","observed_orcids":["https://orcid.org/0009-0009-9987-8828"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ravi Vats","raw_affiliation_strings":["Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020250954","display_name":"Enrico Maria Novelli","orcid":"https://orcid.org/0000-0003-3010-8285","observed_orcids":["https://orcid.org/0000-0003-3010-8285"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Enrico M Novelli","raw_affiliation_strings":["Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5007944034","display_name":"Mark T. Gladwin","orcid":"https://orcid.org/0000-0001-7267-9006","observed_orcids":["https://orcid.org/0000-0001-7267-9006"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mark T Gladwin","raw_affiliation_strings":["Department of Medicine, University of Pittsburgh, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090702301","display_name":"Prithu Sundd","orcid":"https://orcid.org/0000-0001-7568-5719","observed_orcids":["https://orcid.org/0000-0001-7568-5719"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Prithu Sundd","raw_affiliation_strings":["Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5056989880","display_name":"Tirthadipa Pradhan","orcid":"https://orcid.org/0000-0002-8763-4844","observed_orcids":["https://orcid.org/0000-0002-8763-4844"]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tirthadipa Pradhan","raw_affiliation_strings":["University of Pittsburgh, Pittsburgh,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pittsburgh, Pittsburgh,","institution_ids":["https://openalex.org/I170201317"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I170201317"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"136","issue":"Supplement 1","first_page":"16","last_page":"16"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10554","display_name":"Hemoglobinopathies and Related Disorders","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10554","display_name":"Hemoglobinopathies and Related Disorders","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10966","display_name":"Liver physiology and pathology","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12068","display_name":"Neonatal Health and Biochemistry","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2735","display_name":"Pediatrics, Perinatology and Child Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/sickle-cell-disease","display_name":"sickle cell disease","score":0.9980000257492065},{"id":"https://openalex.org/keywords/fxr-signaling","display_name":"FXR signaling","score":0.9129999876022339},{"id":"https://openalex.org/keywords/nf-kappab","display_name":"NF-\u03baB","score":0.7649999856948853},{"id":"https://openalex.org/keywords/liver-injury","display_name":"liver injury","score":0.6940000057220459},{"id":"https://openalex.org/keywords/bile-acid-synthesis","display_name":"bile acid synthesis","score":0.7089999914169312},{"id":"https://openalex.org/keywords/hepatomegaly","display_name":"hepatomegaly","score":0.9079999923706055},{"id":"https://openalex.org/keywords/hyperbilirubinemia","display_name":"hyperbilirubinemia","score":0.9240000247955322},{"id":"https://openalex.org/keywords/fibrosis","display_name":"fibrosis","score":0.6119999885559082},{"id":"https://openalex.org/keywords/gw4064","display_name":"GW4064","score":0.8190000057220459},{"id":"https://openalex.org/keywords/intravital-imaging","display_name":"intravital imaging","score":0.9100000262260437}],"concepts":[{"id":"https://openalex.org/C2776637226","wikidata":"https://www.wikidata.org/wiki/Q6658207","display_name":"Liver injury","level":2,"score":0.5818166732788086},{"id":"https://openalex.org/C2779399885","wikidata":"https://www.wikidata.org/wiki/Q413288","display_name":"Bile acid","level":2,"score":0.49195000529289246},{"id":"https://openalex.org/C203862802","wikidata":"https://www.wikidata.org/wiki/Q14905041","display_name":"Farnesoid X receptor","level":5,"score":0.4843060076236725},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.47380131483078003},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.45894208550453186},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4465333819389343},{"id":"https://openalex.org/C39321552","wikidata":"https://www.wikidata.org/wiki/Q18052005","display_name":"G protein-coupled bile acid receptor","level":3,"score":0.4368836283683777},{"id":"https://openalex.org/C2777075537","wikidata":"https://www.wikidata.org/wiki/Q929737","display_name":"Liver disease","level":2,"score":0.4355849623680115},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3838799297809601},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3535223603248596},{"id":"https://openalex.org/C63932345","wikidata":"https://www.wikidata.org/wiki/Q422500","display_name":"Nuclear receptor","level":4,"score":0.17489758133888245},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.11651545763015747},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.07742685079574585},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood-2020-143330","doi":"https://doi.org/10.1182/blood-2020-143330","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2020-143330","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.98580002784729,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3011765807","https://openalex.org/W4313369179","https://openalex.org/W2989465689","https://openalex.org/W3175418365","https://openalex.org/W4388537382","https://openalex.org/W4405051811","https://openalex.org/W3130438120","https://openalex.org/W4389229320","https://openalex.org/W2588227981","https://openalex.org/W4396229373"],"abstract_inverted_index":{"Hepatic":[0],"crisis":[1,20],"is":[2],"an":[3],"emergent":[4],"complication":[5],"affecting":[6],"sickle":[7,17,170],"cell":[8,18,171],"disease":[9],"(SCD)":[10],"patients,":[11],"however,":[12],"the":[13,36,72,79,135,163],"molecular":[14],"mechanism":[15],"of":[16,38,58,81,84,96,120,153,157,165,178],"hepatobiliary":[19,151],"remains":[21],"poorly":[22],"understood.":[23],"We":[24],"have":[25],"used":[26],"intravital":[27],"imaging":[28],"to":[29,94,137,150,168,180],"show":[30],"that":[31,139],"sinusoidal":[32,113],"ischemia":[33,114],"occurs":[34],"in":[35,71,91,115,129],"liver":[37,50,109,126],"transgenic-humanized":[39],"SCD":[40,45,73,116,130],"mice":[41,46,74],"under":[42],"basal":[43],"condition.":[44],"manifested":[47],"progressive":[48],"hepatomegaly,":[49],"injury":[51,77,110,127,152],"and":[52,68,87,100,111],"hyperbilirubinemia.":[53],"RNA-sequence":[54],"analysis":[55],"identified":[56],"dysregulation":[57],"genes":[59],"encoding":[60],"proteins":[61],"responsible":[62],"for":[63],"fibrosis,":[64],"bile":[65,69,98,101,142,146],"acid":[66],"synthesis,":[67],"transport":[70,99],"liver.":[75],"Live":[76],"was":[78],"result":[80],"NF-\u03baB-dependent":[82],"inhibition":[83],"FXR":[85,121],"signaling":[86],"its":[88],"downstream":[89],"targets":[90],"hepatocytes,":[92],"leading":[93],"loss":[95],"canalicular":[97],"metabolism.":[102],"Blocking":[103],"NF-\u03baB":[104],"activation":[105],"rescued":[106],"FXR-signaling,":[107],"ameliorated":[108,125],"resolved":[112],"mice.":[117,131],"Moreover,":[118],"administration":[119],"agonist":[122],"(GW4064)":[123],"also":[124],"seen":[128],"These":[132],"findings":[133],"are":[134],"first":[136],"identify":[138],"FXR-dependent":[140],"impaired":[141],"secretion":[143],"promotes":[144],"intrahepatic":[145],"accumulation,":[147],"which":[148],"contributes":[149],"SCD.":[154],"Improved":[155],"understanding":[156],"these":[158],"pathways":[159],"could":[160],"potentially":[161],"benefit":[162],"development":[164],"new":[166],"therapies":[167],"treat":[169],"hepatic":[172],"crisis.":[173],"Disclosures":[174],"No":[175],"relevant":[176],"conflicts":[177],"interest":[179],"declare.":[181]},"counts_by_year":[],"updated_date":"2026-10-09T09:14:12.587421","created_date":"2020-11-09T00:00:00"}
