{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:42:33Z","timestamp":1793673753506,"version":"4.5.1"},"reference-count":65,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":54,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["BX003865"],"award-info":[{"award-number":["BX003865"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["BX002182"],"award-info":[{"award-number":["BX002182"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["BX005288"],"award-info":[{"award-number":["BX005288"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK50189"],"award-info":[{"award-number":["DK50189"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013678","name":"Cancer Center, University of Colorado","doi-asserted-by":"crossref","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}],"id":[{"id":"10.13039\/100013678","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:p>\n                    Induction of heme oxygenase-1 (HO-1\/\n                    <jats:italic>Hmox1<\/jats:italic>\n                    ) is broadly considered cytoprotective, but the role of colonic epithelial HO-1 in colitis-associated tumorigenesis is poorly defined. HO-1 catabolizes heme, releasing ferrous iron, a key driver of oxidative stress and lipid peroxidation. We observed that colonic epithelial HO-1 was induced during colitis and tumorigenesis. We also found that HO-1 was upregulated in ferroptosis-inducing conditions in murine and human colonic epithelial organoids and correlated with lipid peroxidation and ferroptosis markers in colonic tumors. In colonic epithelial organoids exposed to heme, deletion of\n                    <jats:italic>Hmox1<\/jats:italic>\n                    amplified a compensatory oxidative stress and detoxification transcriptional program, likely reflecting unresolved oxidative and nonoxidative toxicity from heme. In vivo, epithelial HO-1\u2013deficient mice developed significantly fewer and smaller tumors compared with littermate controls in a colitis-associated tumorigenesis model, despite similar inflammatory injury. Tumors from KO mice exhibited reduced iron levels, decreased lipid peroxidation, lower oxidative DNA damage, and decreased proliferation. Single-cell RNA sequencing of tumor epithelial cells revealed a shift from a proliferative to a stress-adaptive program with loss of HO-1. These findings identify epithelial HO-1 as a context-dependent regulator of tumorigenesis: it is protective against acute heme toxicity but promotes iron-dependent oxidative damage and proliferation in the setting of chronic inflammation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.181032","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:31:27Z","timestamp":1766068287000},"source":"Crossref","is-referenced-by-count":4,"title":["Epithelial HO-1 regulates iron availability and promotes colonic tumorigenesis in a context-dependent manner"],"prefix":"10.1172","volume":"11","author":[{"given":"Rosemary C.","family":"Callahan","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian C.","family":"Curry","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Bhagavatula","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children\u2019s Hospital Colorado; Mucosal Inflammation Program, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-5063","authenticated-orcid":true,"given":"Alyse W.","family":"Staley","sequence":"additional","affiliation":[{"name":"University of Colorado Cancer Center Biostatistics Core, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.M.","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiz","family":"Minhajuddin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rane M.","family":"Neuhart","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children\u2019s Hospital Colorado; Mucosal Inflammation Program, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaikh M.","family":"Atif","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Orlicky","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Cartwright","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Gerich","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calen A.","family":"Steiner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianne L.","family":"Theiss","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H.T.","family":"Hall","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children\u2019s Hospital Colorado; Mucosal Inflammation Program, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0431-8887","authenticated-orcid":true,"given":"Sean P.","family":"Colgan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Onyiah","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32545-0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2012.01.010"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izx104"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199011013231802"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198712243172603"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.12.038"},{"issue":"1\u20132","key":"B7","first-page":"162","article-title":"Hemoglobin and hemin induce DNA damage in human colon tumor cells HT29 clone 19A and in primary human colonocytes","volume":"594","author":"Glei","year":"2006","journal-title":"Mutat Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02950-8"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108181"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03064-6"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00187"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2005"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10919"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e3181fd2aae"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4165"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.01.051"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.003"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216147"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00406-7"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166846"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.154"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00728.x"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002433"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051047"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.12.025"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0794-4"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1342-6"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303333"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(2003)008<0329:EOHSPH>2.0.CO;2"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02775.x"},{"key":"B33","first-page":"S229","article-title":"Increased intestinal expression of heme oxygenase-1 and its localization in patients with ulcerative colitis","volume":"23 Suppl 2","author":"Takagi","year":"2008","journal-title":"J Gastroenterol Hepatol"},{"key":"B34","article-title":"Oxidative stress and lipid peroxidation products in cancer progression and therapy","volume":"2012","author":"Barrera","year":"2012","journal-title":"ISRN Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.06.001"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143691"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2003.tb01386.x"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.59404"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2005.03.004"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19850201)55:3<577::AID-CNCR2820550317>3.0.CO;2-D"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.878920"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104202"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nature24489"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1993.1566"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00044.2017"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5162"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009548"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2022.06.004"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200853RRR"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3846217"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04367-3"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89676"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204935200"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-021-00474-8"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.05.033"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/34.10.2125"},{"issue":"database issue","key":"B58","first-page":"D991","article-title":"NCBI GEO: archive for functional genomics data sets--update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B59","unstructured":"R: A language and environment for statistical computing. R Foundation for Statistical Computing; 2022. https:\/\/www.R-project.org\/"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"B62"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0844-5"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/181032\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:30:44Z","timestamp":1778873444000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/181032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":65,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,12,11]]},"published-print":{"date-parts":[[2026,2,9]]}},"alternative-id":["10.1172\/jci.insight.181032"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.181032","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.03.06.583112","asserted-by":"object"}]},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"article-number":"e181032"}}