{"id":"https://openalex.org/W2979369669","doi":"https://doi.org/10.1182/blood.v124.21.2.2","title":"The Ashwell-Morell Receptor Regulates Hepatic Thrombopoietin Production Via JAK2-STAT3 Signaling in Vivo and in Vitro","display_name":"The Ashwell-Morell Receptor Regulates Hepatic Thrombopoietin Production Via JAK2-STAT3 Signaling in Vivo and in Vitro","publication_year":2014,"publication_date":"2014-12-06","ids":{"openalex":"https://openalex.org/W2979369669","doi":"https://doi.org/10.1182/blood.v124.21.2.2","mag":"2979369669"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v124.21.2.2","doi":"https://doi.org/10.1182/blood.v124.21.2.2","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v124.21.2.2","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":"article","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/A5027616721","display_name":"Renata Grozovsky","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Renata Grozovsky","raw_affiliation_strings":["Brigham and Women's Hospital, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Brigham and Women's Hospital, Boston, MA","institution_ids":["https://openalex.org/I1283280774"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5033084245","display_name":"Antonija Jurak Begonja","orcid":"https://orcid.org/0000-0001-5798-0888","observed_orcids":["https://orcid.org/0000-0001-5798-0888"]},"institutions":[{"id":"https://openalex.org/I154347574","display_name":"University of Rijeka","ror":"https://ror.org/05r8dqr10","country_code":"HR","type":"education","lineage":["https://openalex.org/I154347574"]}],"countries":["HR"],"is_corresponding":true,"raw_author_name":"Antonija Jurak Begonja","raw_affiliation_strings":["Univeristy of Rijeka, Rijeka, Croatia"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Univeristy of Rijeka, Rijeka, Croatia","institution_ids":["https://openalex.org/I154347574"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071191923","display_name":"John H. Hartwig","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John H. Hartwig","raw_affiliation_strings":["Brigham & Women's Hospital, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Brigham & Women's Hospital, Boston, MA","institution_ids":["https://openalex.org/I1283280774"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023521073","display_name":"Herv\u00e9 Falet","orcid":"https://orcid.org/0000-0003-0788-9204","observed_orcids":["https://orcid.org/0000-0003-0788-9204"]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Herve Falet","raw_affiliation_strings":["Brigham and Women's Hospital, Harvard Medical School, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Brigham and Women's Hospital, Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I1283280774","https://openalex.org/I136199984"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5019757442","display_name":"Karin M. Hoffmeister","orcid":"https://orcid.org/0000-0001-6526-7919","observed_orcids":["https://orcid.org/0000-0001-6526-7919"]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Karin M Hoffmeister","raw_affiliation_strings":["Brigham and Women's Hospital, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Brigham and Women's Hospital, Boston, MA","institution_ids":["https://openalex.org/I1283280774"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5033084245"],"corresponding_institution_ids":["https://openalex.org/I154347574"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.2357,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.65847953,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":94},"biblio":{"volume":"124","issue":"21","first_page":"2","last_page":"2"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10746","display_name":"Platelet Disorders and Treatments","score":0.9994999766349792,"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/T10746","display_name":"Platelet Disorders and Treatments","score":0.9994999766349792,"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/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":9.999999747378752e-05,"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/T10993","display_name":"Complement system in diseases","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/asialoglycoprotein-receptor","display_name":"asialoglycoprotein receptor","score":0.8769999742507935},{"id":"https://openalex.org/keywords/thrombopoietin","display_name":"thrombopoietin","score":0.9610000252723694},{"id":"https://openalex.org/keywords/platelet-clearance","display_name":"platelet clearance","score":0.7400000095367432},{"id":"https://openalex.org/keywords/sialic-acid","display_name":"sialic acid","score":0.8199999928474426},{"id":"https://openalex.org/keywords/jak2-stat3-signaling-pathway","display_name":"JAK2/STAT3 signaling","score":0.8740000128746033},{"id":"https://openalex.org/keywords/hepatocytes","display_name":"hepatocytes","score":0.5529999732971191},{"id":"https://openalex.org/keywords/platelet-survival","display_name":"platelet survival","score":0.6970000267028809},{"id":"https://openalex.org/keywords/megakaryocytes","display_name":"megakaryocytes","score":0.9449999928474426},{"id":"https://openalex.org/keywords/megakaryopoiesis","display_name":"megakaryopoiesis","score":0.597000002861023},{"id":"https://openalex.org/keywords/platelet-destruction","display_name":"platelet destruction","score":0.3499999940395355}],"concepts":[{"id":"https://openalex.org/C2777863708","wikidata":"https://www.wikidata.org/wiki/Q424519","display_name":"Thrombopoietin","level":4,"score":0.8645525574684143},{"id":"https://openalex.org/C89560881","wikidata":"https://www.wikidata.org/wiki/Q101026","display_name":"Platelet","level":2,"score":0.7280606031417847},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.5898960828781128},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.588126540184021},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5496621131896973},{"id":"https://openalex.org/C2780115458","wikidata":"https://www.wikidata.org/wiki/Q419311","display_name":"Sialic acid","level":2,"score":0.4848259687423706},{"id":"https://openalex.org/C2776958478","wikidata":"https://www.wikidata.org/wiki/Q14914622","display_name":"Thrombopoiesis","level":5,"score":0.4497402608394623},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.4140506088733673},{"id":"https://openalex.org/C11569505","wikidata":"https://www.wikidata.org/wiki/Q727265","display_name":"Asialoglycoprotein receptor","level":4,"score":0.4123757779598236},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3458242118358612},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.24961599707603455},{"id":"https://openalex.org/C2779705218","wikidata":"https://www.wikidata.org/wiki/Q821701","display_name":"Megakaryocyte","level":4,"score":0.22774749994277954},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.18286588788032532},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.17135891318321228},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.14430469274520874},{"id":"https://openalex.org/C2776200302","wikidata":"https://www.wikidata.org/wiki/Q827450","display_name":"Hepatocyte","level":3,"score":0.1293262243270874},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.12165588140487671},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.09146928787231445},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v124.21.2.2","doi":"https://doi.org/10.1182/blood.v124.21.2.2","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v124.21.2.2","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","id":"https://metadata.un.org/sdg/3","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2570726038","https://openalex.org/W2016057405","https://openalex.org/W2520949122","https://openalex.org/W2404121852","https://openalex.org/W2140547740","https://openalex.org/W3147432370","https://openalex.org/W3116927555","https://openalex.org/W2095481477","https://openalex.org/W2564026348","https://openalex.org/W2399884037"],"abstract_inverted_index":{"Abstract":[0],"The":[1,354,443],"human":[2,318,325,419],"body":[3],"produces":[4],"and":[5,17,44,59,102,152,208,218,266,310,339,343,375,382,418,436,453,469,513,525,530],"removes":[6],"1011":[7],"platelets":[8,81,159,242,295,327,362,502],"daily":[9],"to":[10,126,182,366,455,520,539],"maintain":[11],"a":[12,54,398,427,515],"normal":[13],"steady-state":[14],"platelet":[15,29,38,47,100,123,166,204,219,231,286,526],"count,":[16],"the":[18,34,41,90,111,117,147,161,199,212,234,364,406,410,456,459,509],"level":[19],"of":[20,28,37,46,57,61,138,157,317,360,380,423,450,458,482,494,537],"production":[21,58,527],"can":[22],"be":[23],"greatly":[24],"increased":[25,122,136,192,207,253,271],"under":[26],"conditions":[27],"destruction.":[30],"Thrombopoietin":[31],"(TPO)":[32],"is":[33,206],"primary":[35,510],"regulator":[36],"production,":[39],"supporting":[40],"survival,":[42,124],"proliferation":[43],"differentiation":[45],"precursors,":[48],"bone":[49,267,311],"marrow":[50,268,312],"megakaryocytes.":[51],"Hepatocytes":[52],"are":[53,87,108],"major":[55],"source":[56],"secretion":[60,471],"circulating":[62,67],"TPO.":[63],"However,":[64],"mechanisms":[65],"regulating":[66,99],"TPO":[68,104,175,188,216,220,238,255,264,275,304,307,333,351,368,466,470,488,523],"levels":[69,177,190,217,257,309,524],"have":[70],"been":[71],"debated":[72],"for":[73],"decades.":[74],"Here,":[75],"we":[76,404,499],"provide":[77],"experimental":[78],"evidence":[79],"that":[80,155,501],"lacking":[82,116,198],"sialic":[83,139],"acid":[84],"(desialylated":[85],"platelets)":[86],"removed":[88],"by":[89,143,160,179,193,211,233,279,284,328,337,347,358,363,395,492],"hepatic":[91,103,254],"Ashwell-Morell":[92],"receptor":[93],"(AMR":[94],"or":[95,246],"asialoglycoprotein":[96],"receptor),":[97],"thereby":[98,507],"survival":[101],"levels.":[105,239],"These":[106],"conclusions":[107],"based":[109],"on":[110,303],"following":[112],"evidence:":[113],"1)":[114],"Mice":[115],"AMR":[118,162,235,365,511],"Asgr2":[119],"subunit":[120],"had":[121,174,300],"compared":[125,181],"wild":[127],"type":[128],"(WT)":[129],"mice.":[130,184,228,441],"Platelets":[131],"from":[132,171,244],"Asgr2-null":[133,172,247,298,434],"mice":[134,173,197,248,252,299,435,484],"showed":[135],"loss":[137],"acid,":[140],"as":[141,258,260,393,409,504],"evidenced":[142,394],"flow":[144],"cytometry":[145],"using":[146],"galactose":[148],"specific":[149,399],"lectins":[150],"RCAI":[151],"ECL,":[153],"showing":[154],"removal":[156],"desialylated":[158,203,230,294,326,361,477,496],"regulates":[163],"in":[164,195,225,272,332,350,373,376,389,414,430,433,439,472,528,531],"vivo":[165,374,480,529],"survival.":[167],"2)":[168],"Livers":[169],"isolated":[170,243],"mRNA":[176,189,256,276,305,334,369,467,489],"decreased":[178,448],"40%,":[180],"WT":[183,251,390,483],"In":[185,292,479],"contrast,":[186,293],"liver":[187,237,391,416,424],"were":[191,222,371,385],"30%":[194],"St3gal4-null":[196,245,440],"sialyltransferase":[200],"ST3GalIV,":[201],"where":[202],"clearance":[205],"specifically":[209],"mediated":[210],"AMR.":[213],"Both":[214],"plasma":[215,308,522],"contents":[221],"similarly":[223],"altered":[224],"both":[226],"mutant":[227],"Thus,":[229],"uptake":[232,359],"regulated":[236],"3)":[240],"Desialylated":[241],"infused":[249,296],"into":[250,297],"early":[259],"12h":[261],"post-infusion.":[262,291],"Plasma":[263],"concentrations":[265],"megakaryocyte":[269,313],"numbers":[270],"parallel":[273],"with":[274,324,476,485],"levels,":[277],"peaking":[278],"day":[280,289],"2":[281],"post-infusion,":[282],"followed":[283,346],"new":[285],"release":[287],"at":[288],"10":[290],"no":[301],"effect":[302],"synthesis,":[306],"numbers.":[314],"4)":[315],"Incubation":[316],"hepatoma":[319],"cell":[320],"line,":[321],"HepG2":[322,420,473],"cells,":[323,392],"sialidase":[329],"treatment":[330,481],"resulted":[331],"expression":[335,468],"increase":[336,349,438,490],"2.2":[338],"2.9-fold":[340],"after":[341],"4":[342],"6h,":[344],"respectively,":[345],"significant":[348,437],"secretion.":[352],"5)":[353],"signaling":[355],"pathways":[356],"activated":[357],"induce":[367],"transcription":[370,463],"investigated":[372],"vitro.":[377,532],"Major":[378],"polypeptides":[379],"60-70":[381],"125":[383],"kDa":[384],"highly":[386],"tyrosine":[387,411],"phosphorylated":[388],"SDS-PAGE.":[396],"Using":[397],"antibody":[400],"directed":[401],"against":[402],"JAK2,":[403,451],"identified":[405],"125-kDa":[407],"phosphoprotein":[408],"kinase":[412],"JAK2":[413,431],"mouse":[415],"cells":[417,474],"cells.":[421],"Analysis":[422],"samples":[425],"revealed":[426],"marked":[428],"reduction":[429],"phosphorylation":[432,449,452],"6)":[442],"JAK1/2":[444],"inhibitor":[445],"AZD1480":[446,486],"significantly":[447],"translocation":[454],"nucleus":[457],"acute":[460],"phase":[461],"response":[462],"factor":[464],"STAT3,":[465],"incubated":[475],"platelets.":[478,497],"blocked":[487],"promoted":[491],"injection":[493],"endogenously":[495],"Therefore":[498],"conclude":[500],"desialylate":[503],"they":[505],"circulate,":[506],"becoming":[508],"ligand":[512],"providing":[514],"novel":[516],"physiological":[517],"feedback":[518],"mechanism":[519],"regulate":[521],"Disclosures":[533],"No":[534],"relevant":[535],"conflicts":[536],"interest":[538],"declare.":[540]},"counts_by_year":[{"year":2021,"cited_by_count":1},{"year":2016,"cited_by_count":1}],"updated_date":"2026-10-08T09:06:37.294493","created_date":"2019-10-18T00:00:00"}