{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:13:48Z","timestamp":1792098828383,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJS\u2010186330"],"award-info":[{"award-number":["PJS\u2010186330"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The iron regulatory hormone hepcidin contributes to the pathogenesis of anemia of inflammation (AI) by inhibiting the iron exporter ferroportin in target cells, causing hypoferremia. Under acute inflammation, hepcidin induction requires hemojuvelin (Hjv), a bone morphogenetic protein co\u2010receptor, while <jats:italic>Fpn<\/jats:italic> mRNA is also suppressed in a hepcidin\u2010independent manner. However, it is unclear whether, during chronic inflammation, Hjv and hepcidin\u2010independent <jats:italic>Fpn<\/jats:italic> mRNA regulation are critical for hypoferremia and AI. To address these questions, wild type and <jats:italic>Hjv<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, a model of hemochromatosis, were fed for 8\u2009weeks an adenine\u2010rich diet to develop chronic kidney disease (CKD). Renal inflammation, accessed by increased <jats:italic>Il6<\/jats:italic> mRNA expression, did not differ among genotypes. Hjv disruption did not mitigate the severity of kidney injury but suppressed the inflammatory induction of liver hepcidin. CKD triggered hypoferremia and mild anemia in wild type mice; however, <jats:italic>Hjv<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> littermates maintained high serum iron and normal hemoglobin, consistent with a protective effect of Hjv\/hepcidin deficiency. Notably, tissue <jats:italic>Fpn<\/jats:italic> mRNA levels were not affected by the inflammatory milieu of CKD. Following injection of wild type or <jats:italic>Hjv<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice with heat\u2010killed <jats:styled-content style=\"fixed-case\"><jats:italic>Brucella abortus<\/jats:italic><\/jats:styled-content>, <jats:italic>Fpn<\/jats:italic> mRNA was suppressed during the acute phase of inflammation but quickly recovered and persisted in the chronic phase. We conclude that Hjv deficiency reduces hepcidin levels and mitigates anemia in the CKD model, providing further support for pharmacological targeting of Hjv for the treatment of AI. Moreover, our data demonstrate that <jats:italic>Fpn<\/jats:italic> mRNA suppression only occurs under acute but not chronic inflammatory conditions and therefore cannot substantially contribute to AI pathogenesis.<\/jats:p>","DOI":"10.1002\/ajh.27710","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T07:30:23Z","timestamp":1746862223000},"page":"1323-1333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hypoferremic Response to Chronic Inflammation Is Controlled via the Hemojuvelin\/Hepcidin\/Ferroportin Axis and Does Not Involve Hepcidin\u2010Independent Regulation of <i>Fpn<\/i><scp>mRNA<\/scp>"],"prefix":"10.1002","volume":"100","author":[{"given":"Siqi","family":"Liu","sequence":"first","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiya","family":"Tsyplenkova","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Fillebeen","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-0057","authenticated-orcid":false,"given":"Kostas","family":"Pantopoulos","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-043021-032816"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00745-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013472"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-313064"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-480095"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00104"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-03-841197"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81332"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201485200"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2459"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-595256"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00246.2003"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2422"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060437"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2024.2336128"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-521419"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-521625"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085530"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2011.00010"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1780"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010163"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-012-0937-5"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-018-2531-2"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00089.2016"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00281.2016"},{"key":"e_1_2_10_28_1","volume-title":"StatPearls","author":"Gulhar R.","year":"2025"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050194"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25049"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-024-01086-6"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs569"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S421446"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00896"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2013.05.006"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.4103\/cjp.cjp_13_21"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2012.687375"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.10.018"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.09.003"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2020.11.026"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2018.12.024"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.150433"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-345066"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.140772"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2432"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1747"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-05-786590"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.03.006"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.27710","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T09:03:04Z","timestamp":1759136584000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.27710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,10]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/ajh.27710"],"URL":"https:\/\/doi.org\/10.1002\/ajh.27710","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,10]]},"assertion":[{"value":"2024-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}