{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:59:13Z","timestamp":1790913553784,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Zhejiang province of China","award":["LZ20C170004"],"award-info":[{"award-number":["LZ20C170004"]}]},{"name":"Natural Science Foundation of Zhejiang province of China","award":["LY19H070003"],"award-info":[{"award-number":["LY19H070003"]}]},{"name":"Natural Science Foundation of Zhejiang province of China","award":["226-2022-00023"],"award-info":[{"award-number":["226-2022-00023"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["LZ20C170004"],"award-info":[{"award-number":["LZ20C170004"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["LY19H070003"],"award-info":[{"award-number":["LY19H070003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["226-2022-00023"],"award-info":[{"award-number":["226-2022-00023"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Diabetic nephropathy (DN) is one of the most devastating diabetic microvascular complications. It has previously been observed that iron metabolism levels are abnormal in diabetic patients. However, the mechanism by which iron metabolism levels affect DN is poorly understood. This study was designed to evaluate the role of iron-chelator deferoxamine (DFO) in the improvement of DN. Here, we established a DN rat model induced by diets high in carbohydrates and fat and streptozotocin (STZ) injection. Our data demonstrated that DFO treatment for three weeks greatly attenuated renal dysfunction as evidenced by decreased levels of urinary albumin, blood urea nitrogen, and serum creatinine, which were elevated in DN rats. Histopathological observations showed that DFO treatment improved the renal structures of DN rats and preserved podocyte integrity by preventing the decrease of transcripts of nephrin and podocin. In addition, DFO treatment reduced the overexpression of fibronectin 1, collagen I, IL-1\u03b2, NF-\u03baB, and MCP-1 in DN rats, as well as inflammatory cell infiltrates and collagenous fibrosis. Taken together, our findings unveiled that iron chelation via DFO injection had a protective impact on DN by alleviating inflammation and fibrosis, and that it could be a potential therapeutic strategy for DN.<\/jats:p>","DOI":"10.3390\/biom13081266","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T10:28:48Z","timestamp":1692354528000},"page":"1266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Iron Chelator Deferoxamine Alleviates Progression of Diabetic Nephropathy by Relieving Inflammation and Fibrosis in Rats"],"prefix":"10.3390","volume":"13","author":[{"given":"Yunfei","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jia","sequence":"additional","affiliation":[{"name":"MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Ma","sequence":"additional","affiliation":[{"name":"MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenying","family":"Tian","sequence":"additional","affiliation":[{"name":"MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huahua","family":"Du","sequence":"additional","affiliation":[{"name":"MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1497449","DOI":"10.1155\/2021\/1497449","article-title":"Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment","volume":"2021","author":"Samsu","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nrendo.2013.184","article-title":"Diabetic nephropathy: Diagnosis and treatment","volume":"9","author":"Fineberg","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1053\/j.ajkd.2016.07.004","article-title":"Kidney Disease, Income, and Life Expectancy","volume":"68","author":"Lang","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1007\/s00109-017-1596-3","article-title":"Uncoupled iron homeostasis in type 2 diabetes mellitus","volume":"95","author":"Altamura","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_5","first-page":"1700301","article-title":"Increased Small Intestine Expression of Non-Heme Iron Transporters in Morbidly Obese Patients with Newly Diagnosed Type 2 Diabetes","volume":"62","author":"Becerril","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s12011-018-1446-3","article-title":"Dietary Iron Modulates Glucose and Lipid Homeostasis in Diabetic Mice","volume":"189","author":"Ma","year":"2018","journal-title":"Biol. Trace Element Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E1236","DOI":"10.1152\/ajpendo.00022.2010","article-title":"Dietary iron restriction or iron chelation protects from diabetes and loss of \u03b2-cell function in the obese (ob\/ob lep\u2212\/\u2212) mouse","volume":"298","author":"Cooksey","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00702-012-0795-x","article-title":"Effects of novel neuroprotective and neurorestorative multifunctional drugs on iron chelation and glucose metabolism","volume":"120","author":"Pollak","year":"2012","journal-title":"J. Neural Transm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1080\/10408347.2019.1620095","article-title":"Determination of Iron Chelating Agents by Analytical Methods: A Review","volume":"50","author":"Malik","year":"2020","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/ejh.12507","article-title":"Efficacy and safety of a novel combination of two oral chelators deferasirox\/deferiprone over deferoxamine\/deferiprone in severely iron overloaded young beta thalassemia major patients","volume":"95","author":"Elalfy","year":"2015","journal-title":"Eur. J. Haematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1056\/NEJM199912233412607","article-title":"Disorders of Iron Metabolism","volume":"341","author":"Andrews","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fnagi.2015.00104","article-title":"Intranasal deferoxamine attenuates synapse loss via up-regulating the P38\/HIF-1\u00ce\u00b1 pathway on the brain of APP\/PS1 transgenic mice","volume":"7","author":"Guo","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s12011-009-8377-y","article-title":"Effects of N-Acetylcysteine, Deferoxamine and Selenium on Doxorubicin-Induced Hepatotoxicity","volume":"132","author":"Bulucu","year":"2009","journal-title":"Biol. Trace Element Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/nyas.13174","article-title":"Deferoxamine ameliorates hepatosteatosis via several mechanisms in ob\/ob mice","volume":"1375","author":"Xue","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"738","DOI":"10.2353\/ajpath.2008.070097","article-title":"Iron Depletion by Deferoxamine Up-Regulates Glucose Uptake and Insulin Signaling in Hepatoma Cells and in Rat Liver","volume":"172","author":"Dongiovanni","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.phrs.2005.05.004","article-title":"Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening","volume":"52","author":"Srinivasan","year":"2005","journal-title":"Pharmacol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/1753-0407.12420","article-title":"Effect of the oral iron chelator deferiprone in diabetic nephropathy rats","volume":"9","author":"Zou","year":"2016","journal-title":"J. Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.3389\/fimmu.2019.02594","article-title":"Lipocalin 2 Protects Against Escherichia coli Infection by Modulating Neutrophil and Macrophage Function","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1039\/C9FO02398D","article-title":"Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats","volume":"11","author":"Qi","year":"2020","journal-title":"Food Funct."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S2213-8587(13)70174-8","article-title":"Effects of iron overload on chronic metabolic diseases","volume":"2","author":"Manco","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1172\/JCI35846","article-title":"Hypoxia-inducible factor-1\u03b1 regulates \u03b2 cell function in mouse and human islets","volume":"120","author":"Cheng","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1172\/JCI44421","article-title":"Adipocyte iron regulates adiponectin and insulin sensitivity","volume":"122","author":"Gabrielsen","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1096\/fj.12-216929","article-title":"Iron regulates glucose homeostasis in liver and muscle via AMP-activated protein kinase in mice","volume":"27","author":"Huang","year":"2013","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cell.2014.04.043","article-title":"Heme Oxygenase-1 Drives Metaflammation and Insulin Resistance in Mouse and Man","volume":"158","author":"Jais","year":"2014","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/dmrr.2506","article-title":"Association of iron indices and type 2 diabetes: A meta-analysis of observational studies","volume":"30","author":"Orban","year":"2014","journal-title":"Diabetes\/Metab. Res. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e4641","DOI":"10.1210\/clinem\/dgab454","article-title":"Genetic Support of a Causal Relationship Between Iron Status and Type 2 Diabetes: A Mendelian Randomization Study","volume":"106","author":"Wang","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.bcmd.2015.06.003","article-title":"Experimental animal model to study iron overload and iron chelation and review of other such models","volume":"55","author":"Italia","year":"2015","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1073\/pnas.1413445112","article-title":"Transdermal deferoxamine prevents pressure-induced diabetic ulcers","volume":"112","author":"Duscher","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/s12974-016-0740-2","article-title":"Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction","volume":"13","author":"Li","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.kint.2016.01.012","article-title":"Podocyte injury and its consequences","volume":"89","author":"Nagata","year":"2016","journal-title":"Kidney Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1159\/000072917","article-title":"Podocyte Biology and the Emerging Understanding of Podocyte Diseases","volume":"23","author":"Barisoni","year":"2003","journal-title":"Am. J. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"529","DOI":"10.2215\/CJN.04121206","article-title":"A Proposed Taxonomy for the Podocytopathies: A reassessment of the primary nephrotic diseases","volume":"2","author":"Barisoni","year":"2007","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2615286","DOI":"10.1155\/2017\/2615286","article-title":"Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy","volume":"2017","author":"Dai","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.acc.2021.08.001","article-title":"Nephrinuria and podocytopathies","volume":"108","author":"Kostovska","year":"2022","journal-title":"Adv. Clin. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/2050-7771-2-21","article-title":"Nephrin\u2014A biomarker of early glomerular injury","volume":"2","author":"Kandasamy","year":"2014","journal-title":"Biomark. Res."},{"key":"ref_36","first-page":"83","article-title":"Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria","volume":"39","author":"Kostovska","year":"2019","journal-title":"J. Med. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0002-9440(10)64357-X","article-title":"Podocin Localizes in the Kidney to the Slit Diaphragm Area","volume":"160","author":"Roselli","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41543","DOI":"10.1074\/jbc.C100452200","article-title":"Interaction with Podocin Facilitates Nephrin Signaling","volume":"276","author":"Huber","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18209","DOI":"10.1038\/s41598-020-75320-1","article-title":"Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy","volume":"10","author":"Fukuda","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s13287-022-03121-6","article-title":"Therapeutic potential of conditioned medium obtained from deferoxamine preconditioned umbilical cord mesenchymal stem cells on diabetic nephropathy model","volume":"13","author":"Ozkan","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-981-13-8871-2_4","article-title":"A Glimpse of the Mechanisms Related to Renal Fibrosis in Diabetic Nephropathy","volume":"1165","author":"Zeng","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3748\/wjg.v25.i5.521","article-title":"Iron and liver fibrosis: Mechanistic and clinical aspects","volume":"25","author":"Mehta","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrneph.2014.114","article-title":"Inflammatory processes in renal fibrosis","volume":"10","author":"Meng","year":"2014","journal-title":"Nat. Rev. Nephrol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/8\/1266\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:37:12Z","timestamp":1760128632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/8\/1266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,18]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["biom13081266"],"URL":"https:\/\/doi.org\/10.3390\/biom13081266","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,18]]}}}