{"id":"https://openalex.org/W2991523084","doi":"https://doi.org/10.1182/blood-2019-131921","title":"Sickle Cell Disease Promotes Dysregulation of Hepatic Iron Homeostasis By Regulating Hepcidin Expression","display_name":"Sickle Cell Disease Promotes Dysregulation of Hepatic Iron Homeostasis By Regulating Hepcidin Expression","publication_year":2019,"publication_date":"2019-11-13","ids":{"openalex":"https://openalex.org/W2991523084","doi":"https://doi.org/10.1182/blood-2019-131921","mag":"2991523084"},"language":"en","primary_location":{"id":"doi:10.1182/blood-2019-131921","doi":"https://doi.org/10.1182/blood-2019-131921","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2019-131921","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/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":["Pathology, university of pittsburgh, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pathology, 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":["Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045031054","display_name":"Satdarshan P. Monga","orcid":"https://orcid.org/0000-0002-8437-3378","observed_orcids":["https://orcid.org/0000-0002-8437-3378"]},"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":"Satdarshan Pal Monga","raw_affiliation_strings":["University Of Pittsburgh, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"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":["Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5066832003","display_name":"Gregory James Kato","orcid":"https://orcid.org/0000-0003-4465-3217","observed_orcids":["https://orcid.org/0000-0003-4465-3217"]},"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":"Gregory J Kato","raw_affiliation_strings":["University of Pittsburgh Physicians, Pittsburgh, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Pittsburgh Physicians, Pittsburgh, PA","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":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"134","issue":"Supplement_1","first_page":"958","last_page":"958"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10452","display_name":"Iron Metabolism and Disorders","score":0.8295999765396118,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"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/T10452","display_name":"Iron Metabolism and Disorders","score":0.8295999765396118,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"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/T10554","display_name":"Hemoglobinopathies and Related Disorders","score":0.1687999963760376,"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/T12094","display_name":"Hemoglobin structure and function","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/sickle-cell-disease","display_name":"sickle cell disease","score":0.9990000128746033},{"id":"https://openalex.org/keywords/hepcidin","display_name":"hepcidin","score":0.9729999899864197},{"id":"https://openalex.org/keywords/hif-2alpha","display_name":"HIF-2\u03b1","score":0.8550000190734863},{"id":"https://openalex.org/keywords/hypoxia-signaling","display_name":"hypoxia signaling","score":0.9020000100135803},{"id":"https://openalex.org/keywords/hepatic-iron-accumulation","display_name":"hepatic iron deposition","score":0.7319999933242798},{"id":"https://openalex.org/keywords/liver-injury","display_name":"liver injury","score":0.7459999918937683},{"id":"https://openalex.org/keywords/hemosiderin","display_name":"hemosiderin","score":0.5799999833106995},{"id":"https://openalex.org/keywords/iron-responsive-element","display_name":"iron-responsive element","score":0.8019999861717224},{"id":"https://openalex.org/keywords/hepatobiliary-injury","display_name":"hepatobiliary injury","score":0.6190000176429749},{"id":"https://openalex.org/keywords/therapeutic-target","display_name":"therapeutic target","score":0.5770000219345093},{"id":"https://openalex.org/keywords/prussian-blue-staining","display_name":"Prussian blue staining","score":0.609000027179718}],"concepts":[{"id":"https://openalex.org/C2776768029","wikidata":"https://www.wikidata.org/wiki/Q14882371","display_name":"Hepcidin","level":3,"score":0.975637674331665},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6004068851470947},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5362197160720825},{"id":"https://openalex.org/C2776710925","wikidata":"https://www.wikidata.org/wiki/Q24777245","display_name":"Ferroportin","level":4,"score":0.5128934383392334},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.5068743824958801},{"id":"https://openalex.org/C2777075537","wikidata":"https://www.wikidata.org/wiki/Q929737","display_name":"Liver disease","level":2,"score":0.4747091829776764},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.46515709161758423},{"id":"https://openalex.org/C63645605","wikidata":"https://www.wikidata.org/wiki/Q103191","display_name":"Homeostasis","level":2,"score":0.4462594985961914},{"id":"https://openalex.org/C2776415932","wikidata":"https://www.wikidata.org/wiki/Q48743","display_name":"Western blot","level":3,"score":0.44536441564559937},{"id":"https://openalex.org/C2778319317","wikidata":"https://www.wikidata.org/wiki/Q22327449","display_name":"Ferritin","level":2,"score":0.4405498802661896},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.32381200790405273},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.21822264790534973},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.16516488790512085},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.075569748878479}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood-2019-131921","doi":"https://doi.org/10.1182/blood-2019-131921","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2019-131921","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":[{"display_name":"Good health and well-being","score":0.9763000011444092,"id":"https://metadata.un.org/sdg/3"}],"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/W3096062900","https://openalex.org/W4310108064","https://openalex.org/W3004662402","https://openalex.org/W4382726425","https://openalex.org/W2729940697","https://openalex.org/W3038956807","https://openalex.org/W2799863483","https://openalex.org/W2588876345","https://openalex.org/W2578262820","https://openalex.org/W3175418365"],"abstract_inverted_index":{"Sickle":[0],"cell":[1],"disease":[2],"(SCD)":[3],"is":[4,33,245,261,267],"an":[5,189,275,351],"autosomal-recessive-genetic":[6],"disorder":[7],"that":[8,45,304],"affects":[9,17],"millions":[10],"of":[11,19,66,95,104,108,126,144,159,167,195,204,222,230,283,300,316,325,333,358,376],"people":[12],"worldwide.":[13],"Although":[14],"hepatic":[15,61,128,334],"crisis":[16],"10-40%":[18],"hospitalized":[20],"SCD":[21,48,70,97,115,120,168,196,223,239,301,314],"patients":[22,240],"and":[23,36,60,80,92,130,379],"can":[24],"progress":[25],"to":[26,135,171,178,242,248,269,310],"fatal":[27],"liver":[28,51,71,98,116,166,194,221,299],"failure,":[29],"the":[30,37,90,96,119,141,165,180,193,220,258,280,298,323,356,374],"current":[31],"treatment":[32],"primarily":[34],"supportive":[35],"molecular":[38],"pathophysiology":[39],"remains":[40],"largely":[41],"unknown.":[42],"We":[43,139],"found":[44],"transgenic,":[46],"humanized":[47],"mice":[49,121,169,173,224],"developed":[50],"injury":[52,312,335],"with":[53],"age,":[54],"manifested":[55],"by":[56,74,151,225,272],"increased":[57,86],"inflammation,":[58],"necrosis":[59],"iron":[62,67,87,105,132,149,273,276,295,306],"accumulation.":[63],"The":[64],"presence":[65],"particles":[68],"in":[69,89,102,114,148,164,185,192,214,219,235,257,294,297,313,331,336,361],"was":[72,111,162],"confirmed":[73,234],"transmission":[75],"electron":[76],"micrograph":[77],"(TEM)":[78],"analysis":[79,191,209],"prussian":[81],"blue":[82],"staining":[83],"which":[84],"revealed":[85,210],"accumulation":[88],"central":[91],"midzonal":[93],"region":[94],"tissue.":[99,117],"An":[100],"increase":[101,213],"aggregates":[103],"pigment":[106],"reminiscent":[107],"hemosiderin-laden":[109],"macrophages":[110],"also":[112,122,233,321],"observed":[113,163],"Interestingly,":[118,153],"showed":[123,201],"significant":[124,202,212,292],"enrichment":[125],"both":[127],"(p=0.02)":[129],"serum":[131,236],"(p=0.04)":[133],"compared":[134,170,241],"control":[136,172],"AS":[137],"mice.":[138,197],"determined":[140],"expression":[142,157,256],"level":[143,158],"genes":[145],"commonly":[146],"involved":[147],"homeostasis":[150,296,307],"RT-PCR.":[152],"a":[154,211,291],"significantly":[155],"lower":[156],"hepcidin":[160,183,255,326],"transcripts":[161],"(AS)":[174],"(p=0.01).":[175],"In":[176,286],"order":[177],"define":[179],"pathways":[181],"controlling":[182],"transcription":[184],"SCD,":[186],"we":[187],"performed":[188],"RNA-seq":[190],"Remarkably,":[198],"our":[199,288],"data":[200],"misexpression":[203],"hypoxia":[205],"signaling":[206],"pathways.":[207],"Further":[208],"hypoxia-inducible":[215],"factor":[216],"(HIF)-2\u03b1":[217],"levels":[218,229],"western":[226],"blot.":[227],"Reduced":[228],"Hepcidin":[231],"were":[232],"samples":[237],"from":[238],"controls.":[243],"Work":[244],"currently":[246],"underway":[247],"understand":[249],"how":[250],"HIF2\u03b1":[251],"might":[252],"hypothetically":[253],"regulate":[254],"liver.":[259],"This":[260],"particularly":[262],"relevant":[263],"because":[264],"HIF2a":[265],"translation":[266],"known":[268],"be":[270],"regulated":[271],"through":[274],"response":[277],"element":[278],"at":[279],"5'":[281],"end":[282],"its":[284],"transcript.":[285],"summary,":[287],"results":[289],"reveal":[290],"defect":[293],"mice,":[302],"suggesting":[303],"impaired":[305],"may":[308],"contribute":[309],"hepatobiliary":[311],"independent":[315],"blood":[317],"transfusions.":[318],"Our":[319],"study":[320],"highlights":[322],"importance":[324],"as":[327,382],"potential":[328],"therapeutic":[329],"target":[330],"regulation":[332],"SCD.":[337],"Disclosures":[338],"Gladwin:":[339],"Bayer":[340],"Pharmaceuticals:":[341],"Other:":[342],"Co-investigator;":[343],"United":[344],"Therapeutics:":[345,390],"Patents":[346,368],"&":[347,369],"Royalties:":[348,370],"Co-inventor":[349],"on":[350],"NIH":[352],"government":[353],"patent":[354],"for":[355,373,384],"use":[357,375],"nitrite":[359],"salts":[360],"cardiovascular":[362],"diseases":[363],";":[364],"Globin":[365],"Solutions,":[366],"Inc:":[367],"Provisional":[371],"patents":[372],"recombinant":[377],"neuroglobin":[378],"heme-based":[380],"molecules":[381],"antidotes":[383],"CO":[385],"poisoning.":[386],"Kato:Novartis,":[387],"Global":[388],"Blood":[389],"Consultancy,":[391],"Research":[392,395],"Funding;":[393],"Bayer:":[394],"Funding.":[396]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-10-09T09:14:12.587421","created_date":"2019-12-05T00:00:00"}
