{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:25:28Z","timestamp":1790724328405,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81630068"],"award-info":[{"award-number":["81630068"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670881"],"award-info":[{"award-number":["31670881"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Immune responses contribute to a large extent to heart diseases. However, it is still not clear how the key inflammatory mediator interferon\u2010\u03b3 (IFN\u03b3) plays a role in doxorubicin (DOX)\u2010induced cardiomyopathy. We report here that DOX\u2010induced heart dysfunction involves IFN\u03b3 signaling in mice. The IFN\u03b3 receptor was found to be highly expressed on cardiomyocytes, and its downstream signaling was activated in heart tissues upon DOX treatment.\n                    <jats:italic>In vitro,<\/jats:italic>\n                    IFN\u03b3 strongly aggravated the injury of cardiomyocytes exposed to DOX. Although not affecting DOX\u2010induced cell death, IFN\u03b3 disrupted mitochondrial respiration and fatty acid oxidation in DOX\u2010exposed cardiomyocytes. IFN\u03b3 extended the suppression of the AMP\u2010activated protein kinase (AMPK)\/acetyl\u2010CoA carboxylase (ACC) axis by DOX to a p38\u2010dependent branch. Activation of AMPK or inhibition of p38 inhibited the enhancing effect of IFN\u03b3 on the DOX\u2010induced cardiotoxicity and prolonged the survival time in DOX\u2010treated mice. Taken together, our results indicate that reprogramming of cardiac metabolism by IFN\u03b3 represents a previously unidentified key step for DOX\u2010induced cardiomyopathy. This unavoidable impact of IFN\u03b3 on cardiomyocyte metabolism during chemotherapy redirects our attention to the balance between beneficial immunosurveillance of cancer cells and unwanted toxic side\u2010effects. Copyright \u00a9 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.5192","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T03:39:33Z","timestamp":1542166773000},"page":"320-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Doxorubicin\u2010induced cardiotoxicity involves IFN\u03b3\u2010mediated metabolic reprogramming in cardiomyocytes"],"prefix":"10.1002","volume":"247","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7993-8055","authenticated-orcid":false,"given":"Chen","family":"Ni","sequence":"first","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou University  Zhengzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein and Peptide Pharmaceuticals, CAS\u2010University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences University of the Chinese Academy of Sciences  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou University  Zhengzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Lou","sequence":"additional","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou University  Zhengzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou University  Zhengzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein and Peptide Pharmaceuticals, CAS\u2010University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences University of the Chinese Academy of Sciences  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xue","sequence":"additional","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou University  Zhengzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingolf","family":"Blasig","sequence":"additional","affiliation":[{"name":"Leibniz Institut f\u00fcr Molekulare Pharmakologie  Berlin\u2010Buch Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Erben","sequence":"additional","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou University  Zhengzhou PR China"},{"name":"Key Laboratory of Protein and Peptide Pharmaceuticals, CAS\u2010University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences University of the Chinese Academy of Sciences  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9793-7964","authenticated-orcid":false,"given":"Zhihai","family":"Qin","sequence":"additional","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou University  Zhengzhou PR China"},{"name":"Key Laboratory of Protein and Peptide Pharmaceuticals, CAS\u2010University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences University of the Chinese Academy of Sciences  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-070213-054849"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.40.1273"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003688"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4087"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11407"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdf167"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.016704"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-059"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0064-0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2015.03.005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000146889.46519.27"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.01.004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.11.1549"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80218-6"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4340"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050915"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2008.01.004"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/annotation\/e82f77a8-3d29-44be-a9ef-7abc6c7e584a"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-013-9393-8"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.08.040"},{"key":"e_1_2_7_22_1","first-page":"3730","article-title":"The CO\/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy","volume":"117","author":"Suliman HB","year":"2007","journal-title":"J Clin Invest"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2919"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72931"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-012-0304-5"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.055095"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.04.006"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2010.12.002"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.03.006"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.303633"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.159.5.1560"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.08.019"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.202"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056843"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3311"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.774745"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2216"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.10.012"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000121354.34067.48"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-003-0391-x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.2.165"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2010.01.019"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2015.11.004"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414665111"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.03.012"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4907"},{"key":"e_1_2_7_47_2","first-page":"25.3.1","article-title":"Assessment of fatty acid beta oxidation in cells and isolated mitochondria","volume":"60","author":"Rogers GW","year":"2018","journal-title":"Curr Protoc Toxicol"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.5192","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5192","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5192","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:43:16Z","timestamp":1760960596000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,24]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1002\/path.5192"],"URL":"https:\/\/doi.org\/10.1002\/path.5192","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,24]]},"assertion":[{"value":"2018-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}