{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:33:07Z","timestamp":1789011187675,"version":"build-2803163510"},"reference-count":123,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","award":["Scholar Award"],"award-info":[{"award-number":["Scholar Award"]}],"id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK125617"],"award-info":[{"award-number":["DK125617"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:p>Sickle cell disease (SCD) is an autosomal recessive genetic disorder that affects \u223c100,000 Americans and millions of people worldwide. Erythrocyte sickling, vaso-occlusion, sterile inflammation, and hemolysis are the major pathophysiological pathways leading to liver injury in SCD. Although hepatic dysfunction affects up to 10%\u201340% of patients with SCD, therapeutic approaches to prevent liver injury in SCD are not known, and the molecular mechanisms promoting progressive liver injury in SCD remain poorly understood. Animal models have been beneficial in bridging the gap between preclinical and translational research in SCD. Recent advances in methodology have allowed the development of several humanized animal models to address various aspects of SCD-related liver diseases. This review provides an overview of current knowledge of the molecular mechanisms and potential therapeutic options of SCD-associated liver dysfunction using the Townes mouse model.<\/jats:p>","DOI":"10.1152\/ajpcell.00175.2022","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T13:19:34Z","timestamp":1656335974000},"page":"C494-C504","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular mechanisms of hepatic dysfunction in sickle cell disease: lessons from Townes mouse model"],"prefix":"10.1152","volume":"323","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-4844","authenticated-orcid":true,"given":"Tirthadipa","family":"Pradhan-Sundd","sequence":"first","affiliation":[{"name":"Pittsburgh Heart, Liver and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"},{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Kato","sequence":"additional","affiliation":[{"name":"CSL Behring, King of Prussia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8285","authenticated-orcid":true,"given":"Enrico M.","family":"Novelli","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Liver and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"},{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61682-2"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2010.02.016"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61029-X"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012838"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2015.12.016"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05432.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.10.900"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60692-4"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00435"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7424.1151"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201111-2082CI"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0948"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1005565"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph1008"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200202270-00022"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05476.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(71)90429-6"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2011.01647.x"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4021\/gr2009.12.1327"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2019000037"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.08.009"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2020.08.003"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.24114"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(86)90276-3"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31239"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v8.i3.108"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08961.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2013.11.003"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228399"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/761740"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002886"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.290.6470.744"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.12659\/AJCR.895218"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14462"},{"key":"B35","first-page":"1183","volume":"98","author":"Costa DB","year":"2006","journal-title":"J Natl Med Assoc"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2015-210166"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20971"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000184446.52454.69"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9270(99)00616-4"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-005-0005-z"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2006.04.007"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2003000300006"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/v12030302"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2009.006"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14575"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2010.01449.x"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89761"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1084\/JEM.20200065"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018024299"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-625707"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002653"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.256"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00408.2021"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08977.x"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5339.876"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.24.12150"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3719"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3313"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20143"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2839"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v124.21.1373.1373"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-02-004812"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000172"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-131915"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2019.04.022"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v7.i6.691"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009779"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.tracli.2019.02.004"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-08-663245"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/nri2873"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.213"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.01.011"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2017.037"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13347"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1046\/j.1423-0410.2000.79402651.x"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830420116"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1002\/lt.22257"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/272940"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1159\/000243802"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1996.tb01840.x"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v2.i8.302"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26648"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2020.100866"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104742"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3945\/an.116.013961"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32701"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63924"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1007\/s11834-010-0139-9"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31342"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/ng1777"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20616"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2008.003152"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3109\/03630269.2012.721151"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2018.00103"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1586\/ehm.10.2"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.066530"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304577"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25103"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.561917"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2021.1935854"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-127161"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.130179"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-08-868893"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i34.5069"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002298107"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.645593"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201439245"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1080\/10715760802244768"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1002\/jhbp.245"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109445"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.4021\/gr2010.01.1332"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2016.08.130"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.126631"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000603"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2013.11.007"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1111\/j.1549-8719.2011.00090.x"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.211615"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v112.11.sci-44.sci-44"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v122.21.318.318"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490437559"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611770"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.01.003"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/nature15367"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00175.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T11:14:29Z","timestamp":1718622869000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00175.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,1]]},"references-count":123,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,8,1]]}},"alternative-id":["10.1152\/ajpcell.00175.2022"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00175.2022","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,1]]},"assertion":[{"value":"2022-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}