{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:42Z","timestamp":1760146902208,"version":"build-2065373602"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T00:00:00Z","timestamp":1734134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Collaborative Research Centre PolyTarget 1278-2021","doi-asserted-by":"publisher","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Hemolytic-uremic syndrome (HUS) is a systemic complication of an infection with Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli, primarily leading to acute kidney injury (AKI) and microangiopathic hemolytic anemia. Although free heme has been found to aggravate renal damage in hemolytic diseases, the relevance of the heme-degrading enzyme heme oxygenase-1 (HO-1, encoded by Hmox1) in HUS has not yet been investigated. We hypothesized that HO-1, also important in acute phase responses in damage and inflammation, contributes to renal pathogenesis in HUS. The effect of tamoxifen-induced Hmox1 gene deletion on renal HO-1 expression, disease progression and AKI was investigated in mice 7 days after HUS induction. Renal HO-1 levels were increased in Stx-challenged mice with tamoxifen-induced Hmox1 gene deletion (Hmox1R26\u0394\/\u0394) and control mice (Hmox1lox\/lox). This HO-1 induction was significantly lower (\u221243%) in Hmox1R26\u0394\/\u0394 mice compared to Hmox1lox\/lox mice with HUS. Notably, the reduced renal HO-1 expression was associated with an exacerbation of kidney injury in mice with HUS as indicated by a 1.7-fold increase (p = 0.02) in plasma neutrophil gelatinase-associated lipocalin (NGAL) and a 1.3-fold increase (p = 0.06) in plasma urea, while other surrogate parameters for AKI (e.g., periodic acid Schiff staining, kidney injury molecule-1, fibrin deposition) and general disease progression (HUS score, weight loss) remained unchanged. These results indicate a potentially protective role of HO-1 in the pathogenesis of Stx-mediated AKI in HUS.<\/jats:p>","DOI":"10.3390\/toxins16120543","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T10:08:53Z","timestamp":1734343733000},"page":"543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduction in Renal Heme Oxygenase-1 Is Associated with an Aggravation of Kidney Injury in Shiga Toxin-Induced Murine Hemolytic-Uremic Syndrome"],"prefix":"10.3390","volume":"16","author":[{"given":"Antonio N.","family":"Mestekemper","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Pirschel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Krieg","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria K.","family":"Paulmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6803-4755","authenticated-orcid":false,"given":"Christoph","family":"Daniel","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Amann","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-0006","authenticated-orcid":false,"given":"Sina M.","family":"Coldewey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"},{"name":"Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07747 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fruth, A., Lang, C., Gr\u00f6\u00dfl, T., Garn, T., and Flieger, A. (2024). Genomic surveillance of STEC\/EHEC infections in Germany 2020 to 2022 permits insight into virulence gene profiles and novel O-antigen gene clusters. Int. J. Med. Microbiol., 314.","DOI":"10.1016\/j.ijmm.2024.151610"},{"key":"ref_2","first-page":"345","article-title":"Surveillance of Shiga toxin-producing Escherichia coli associated bloody diarrhea in Argentina","volume":"55","author":"Rivas","year":"2023","journal-title":"Rev. Argent. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.33073\/pjm-2024-016","article-title":"Epidemiological Characteristics of Shiga Toxin-Producing Escherichia coli Responsible for Infections in the Polish Pediatric Population","volume":"73","author":"Wierzbicka","year":"2024","journal-title":"Pol. J. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0140-6736(17)30062-4","article-title":"Haemolytic uraemic syndrome","volume":"390","author":"Fakhouri","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1046\/j.1523-1755.2001.060003831.x","article-title":"Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura","volume":"60","author":"Ruggenenti","year":"2001","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liu, Y., Thaker, H., Wang, C., Xu, Z., and Dong, M. (2022). Diagnosis and Treatment for Shiga Toxin-Producing Escherichia coli Associated Hemolytic Uremic Syndrome. Toxins, 15.","DOI":"10.3390\/toxins15010010"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1007\/s00467-022-05851-4","article-title":"Long-term kidney outcomes in non-dialyzed children with Shiga-toxin Escherichia coli associated hemolytic uremic syndrome","volume":"38","author":"Alconcher","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"51ra71","DOI":"10.1126\/scitranslmed.3001118","article-title":"A central role for free heme in the pathogenesis of severe sepsis","volume":"2","author":"Larsen","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e96910","DOI":"10.1172\/jci.insight.96910","article-title":"Intravascular hemolysis activates complement via cell-free heme and heme-loaded microvesicles","volume":"3","author":"Merle","year":"2018","journal-title":"JCI Insight"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1093\/infdis\/jiw357","article-title":"Alterations in Systemic Extracellular Heme and Hemopexin Are Associated With Adverse Clinical Outcomes in Ugandan Children With Severe Malaria","volume":"214","author":"Elphinstone","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1182\/blood-2017-12-819870","article-title":"HO-1(hi) patrolling monocytes protect against vaso-occlusion in sickle cell disease","volume":"131","author":"Liu","year":"2018","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1172\/JCI26857","article-title":"Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice","volume":"116","author":"Belcher","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1177\/15353702231157920","article-title":"Assessment of total and unbound cell-free heme in plasma of patients with sickle cell disease","volume":"248","author":"Vissa","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gbotosho, O.T., Kapetanaki, M.G., and Kato, G.J. (2020). The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.561917"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41577-020-00491-x","article-title":"Regulation of inflammation by the antioxidant haem oxygenase 1","volume":"21","author":"Campbell","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1152\/physrev.00011.2005","article-title":"Heme oxygenase-1\/carbon monoxide: From basic science to therapeutic applications","volume":"86","author":"Ryter","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.pharmtox.010909.105600","article-title":"Mechanisms of cell protection by heme oxygenase-1","volume":"50","author":"Gozzelino","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ryter, S.W. (2022). Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders. Antioxidants, 11.","DOI":"10.3390\/antiox11030555"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dutra, F.F., and Bozza, M.T. (2014). Heme on innate immunity and inflammation. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00115"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1182\/blood-2015-08-663245","article-title":"Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease","volume":"127","author":"Vinchi","year":"2016","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15837","DOI":"10.1073\/pnas.0903419106","article-title":"Heme oxygenase-1 affords protection against noncerebral forms of severe malaria","volume":"106","author":"Seixas","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s12936-020-03305-6","article-title":"Haem oxygenase protects against thrombocytopaenia and malaria-associated lung injury","volume":"19","author":"Ferreira","year":"2020","journal-title":"Malar. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.kint.2021.12.024","article-title":"Divergent roles of haptoglobin and hemopexin deficiency for disease progression of Shiga-toxin-induced hemolytic-uremic syndrome in mice","volume":"101","author":"Pirschel","year":"2022","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wijnsma, K.L., Veissi, S.T., de Wijs, S., van der Velden, T., Volokhina, E.B., Wagener, F., van de Kar, N., and van den Heuvel, L.P. (2020). Heme as Possible Contributing Factor in the Evolvement of Shiga-Toxin Escherichia coli Induced Hemolytic-Uremic Syndrome. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.547406"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1053\/j.ajkd.2016.10.006","article-title":"AJKD Atlas of Renal Pathology: Thrombotic Microangiopathy","volume":"68","author":"Lusco","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6977","DOI":"10.1021\/bi020647r","article-title":"Mechanism of low-density lipoprotein oxidation by hemoglobin-derived iron","volume":"42","author":"Grinshtein","year":"2003","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1182\/blood.V99.11.4160","article-title":"Neutrophil activation by heme: Implications for inflammatory processes","volume":"99","author":"Arruda","year":"2002","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1182\/blood.V98.6.1802","article-title":"Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase","volume":"98","author":"Wagener","year":"2001","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1172\/JCI11218","article-title":"Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors","volume":"107","author":"Kaide","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1084\/jem.192.7.1015","article-title":"Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis","volume":"192","author":"Brouard","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ryter, S.W. (2021). Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115509"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5171","DOI":"10.1073\/pnas.0813132106","article-title":"Bilirubin and glutathione have complementary antioxidant and cytoprotective roles","volume":"106","author":"Sedlak","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109199","DOI":"10.1016\/j.thromres.2024.109199","article-title":"Counteraction of unconjugated bilirubin against heme-induced toxicity in platelets","volume":"244","author":"Manikanta","year":"2024","journal-title":"Thromb. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1186\/s40001-024-01963-9","article-title":"Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: Insights from NHANES data (2009\u20132018)","volume":"29","author":"Huang","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1097\/01.ASN.0000138547.51867.43","article-title":"Verotoxin (shiga toxin) sensitizes renal epithelial cells to increased heme toxicity: Possible implications for the hemolytic uremic syndrome","volume":"15","author":"Bitzan","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.4049\/jimmunol.180.8.5720","article-title":"Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes","volume":"180","author":"Vareille","year":"2008","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1128\/IAI.00592-08","article-title":"Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-Stx2 antibody","volume":"76","author":"Sauter","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dennhardt, S., Pirschel, W., Wissuwa, B., Daniel, C., Gunzer, F., Lindig, S., Medyukhina, A., Kiehntopf, M., Rudolph, W.W., and Zipfel, P.F. (2018). Modeling Hemolytic-Uremic Syndrome: In-Depth Characterization of Distinct Murine Models Reflecting Different Features of Human Disease. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01459"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kumar, R., Mao, Y., Patial, S., and Saini, Y. (2022). Induction of whole-body gene deletion via R26-regulated tamoxifen-inducible Cre recombinase activity. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1018798"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ilchuk, L.A., Stavskaya, N.I., Varlamova, E.A., Khamidullina, A.I., Tatarskiy, V.V., Mogila, V.A., Kolbutova, K.B., Bogdan, S.A., Sheremetov, A.M., and Baulin, A.N. (2022). Limitations of Tamoxifen Application for In Vivo Genome Editing Using Cre\/ER(T2) System. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214077"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"F385","DOI":"10.1152\/ajprenal.00335.2015","article-title":"Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury","volume":"310","author":"Bolisetty","year":"2016","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/intimm\/dxl116","article-title":"Heme oxygenase-1 is not required for mouse regulatory T cell development and function","volume":"19","author":"Zelenay","year":"2006","journal-title":"Int. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1161\/01.CIR.103.12.1695","article-title":"H(mox-1) constitutes an adaptive response to effect antioxidant cardioprotection: A study with transgenic mice heterozygous for targeted disruption of the Heme oxygenase-1 gene","volume":"103","author":"Yoshida","year":"2001","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rana, M., Choubey, P., Nandi, G., Jain, S., Bajaj, D., Sharma, S., and Basu-Modak, S. (2023). Expression of angiogenic factors in the placenta of heme oxygenase-1 deficient mouse embryo. Reprod. Biol., 23.","DOI":"10.1016\/j.repbio.2023.100822"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/biolre\/ioaa057","article-title":"Using ultrasound to define the time point of intrauterine growth retardation in a mouse model of heme oxygenase-1 deficiency\u2020","volume":"103","author":"Meyer","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cca.2022.08.029","article-title":"Neutrophil gelatinase-associated lipocalin (NGAL) in kidney injury\u2014A systematic review","volume":"536","author":"Marakala","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s13054-022-04223-6","article-title":"Comparative accuracy of biomarkers for the prediction of hospital-acquired acute kidney injury: A systematic review and meta-analysis","volume":"26","author":"Pan","year":"2022","journal-title":"Crit. Care"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/CCM.0b013e318195846e","article-title":"Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery--a prospective cohort study","volume":"37","author":"Bellomo","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/hep.27447","article-title":"Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: A critical role for IL-6\/STAT3","volume":"61","author":"Xu","year":"2015","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6630","DOI":"10.4049\/jimmunol.171.12.6630","article-title":"Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1 beta, but not by TNF-alpha","volume":"171","author":"Cowland","year":"2003","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/labinvest.2013.1","article-title":"Bacteroides fragilis enterotoxin upregulates lipocalin-2 expression in intestinal epithelial cells","volume":"93","author":"Yoo","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm1586","article-title":"Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria","volume":"13","author":"Pamplona","year":"2007","journal-title":"Nat. Med."},{"key":"ref_53","first-page":"613","article-title":"Kidney injury by cyclosporine A is aggravated in heme oxygenase-1 deficient mice and involves regulation of microRNAs","volume":"65","author":"Mucha","year":"2018","journal-title":"Acta Biochim. Pol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1172\/JCI4165","article-title":"Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency","volume":"103","author":"Yachie","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_55","first-page":"300","article-title":"Post-mortem Diagnosis of Heme Oxygenase-1 Deficiency by Whole Exome Sequencing in an Iranian Child","volume":"8","author":"Tahghighi","year":"2019","journal-title":"Int. J. Mol. Cell Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12969-020-00474-1","article-title":"Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares","volume":"18","author":"Chau","year":"2020","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10919","DOI":"10.1073\/pnas.94.20.10919","article-title":"Heme oxygenase 1 is required for mammalian iron reutilization","volume":"94","author":"Poss","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bednarz, A., Lipi\u0144ski, P., Starzy\u0144ski, R.R., Tomczyk, M., Kraszewska, I., Herman, S., Kowalski, K., Gruca, E., Jo\u0144czy, A., and Mazgaj, R. (2020). Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207754"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.freeradbiomed.2023.05.018","article-title":"Co-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency","volume":"205","author":"Kopacz","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0002-9440(10)62319-X","article-title":"Plasma protein haptoglobin modulates renal iron loading","volume":"166","author":"Fagoonee","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3390\/toxins4111261","article-title":"Shiga toxins and the pathophysiology of hemolytic uremic syndrome in humans and animals","volume":"4","author":"Mayer","year":"2012","journal-title":"Toxins"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"108317","DOI":"10.1016\/j.celrep.2020.108317","article-title":"Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance","volume":"33","author":"Iniguez","year":"2020","journal-title":"Cell Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"705","DOI":"10.7326\/0003-4819-109-9-705","article-title":"Illnesses associated with Escherichia coli O157:H7 infections. A broad clinical spectrum","volume":"109","author":"Griffin","year":"1988","journal-title":"Ann. Intern. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ab.2013.05.027","article-title":"Stain-Free total protein staining is a superior loading control to \u03b2-actin for Western blots","volume":"440","author":"Gilda","year":"2013","journal-title":"Anal. Biochem."},{"key":"ref_67","unstructured":"R Core Team (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/12\/543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:55:29Z","timestamp":1760115329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/12\/543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,14]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["toxins16120543"],"URL":"https:\/\/doi.org\/10.3390\/toxins16120543","relation":{},"ISSN":["2072-6651"],"issn-type":[{"type":"electronic","value":"2072-6651"}],"subject":[],"published":{"date-parts":[[2024,12,14]]}}}