{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:42:25Z","timestamp":1791466945017,"version":"4.3.4"},"reference-count":53,"publisher":"SAGE Publications","issue":"4-6","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LQ23H290002"],"award-info":[{"award-number":["LQ23H290002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Project of Zhejiang Chinese Medical University","award":["2024JKZKTS02"],"award-info":[{"award-number":["2024JKZKTS02"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82104849"],"award-info":[{"award-number":["82104849"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82274230"],"award-info":[{"award-number":["82274230"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants & Redox Signaling"],"published-print":{"date-parts":[[2026,2]]},"abstract":"\n Aims:<\/jats:title>\n Ferroptosis has been implicated in the pathogenesis of lupus nephritis (LN), yet its precise role and mechanisms remain unclear. This study aimed to clarify the role of ferroptosis in LN progression and its underlying mechanisms.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Transmission electron microscopy (TEM) was used to assess mitochondrial morphology in renal tissues from LN patients and MRL\/\n lpr<\/jats:italic>\n mice. Multidimensional mass spectrometry-based shotgun lipidomics was applied to analyze lipid alterations in renal cortex, medulla, and isolated renal tubules. Immunoblotting and reverse transcription quantitative PCR were performed to evaluate ferroptosis-related proteins and their messenger RNAs (mRNAs). Primary renal tubular epithelial cells (RTECs) from the distinct renal regions (cortex\/medulla) were isolated and exposed to oxidative stress\n in vitro<\/jats:italic>\n . Ferroptosis inducer erastin and inhibitor ferrostatin-1 (Fer-1) were used\n in\u00a0vivo<\/jats:italic>\n to determine causal effects.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n TEM revealed typical ferroptotic mitochondrial changes in renal tissues from both LN patients and lupus-prone mice. In MRL\/\n lpr<\/jats:italic>\n mice, ferroptosis occurred as early as the pre-LN stage (8 weeks) and worsened by 14 weeks, with cortical tubules showing more severe damage than medullary tubules. Lipidomics demonstrated significant increases in lysophospholipids (\n e.g.,<\/jats:italic>\n 22:4 lysophosphatidylethanolamine,\n p<\/jats:italic>\n < 0.001; 20:4 lysophosphatidylcholine,\n p<\/jats:italic>\n < 0.01) and HNE species (\n p<\/jats:italic>\n < 0.05), along with reductions in plasmalogens (\n e.g.,<\/jats:italic>\n 18:1\u201320:4 plasmenylcholine,\n p<\/jats:italic>\n < 0.001). Mechanistically, ferroptosis was driven by downregulation of glutathione peroxidase 4 (\n p<\/jats:italic>\n < 0.001) and solute carrier family 7 member 11 (\n p<\/jats:italic>\n < 0.01) and upregulation of Acyl-CoA synthetase long chain family member 4 (\n p<\/jats:italic>\n < 0.05), consistent with mRNA changes. Functionally, cortical RTECs cultured\n in vitro<\/jats:italic>\n exhibited higher lipid reactive oxygen species (\n p<\/jats:italic>\n < 0.001) and ferrous ion (Fe\n 2+<\/jats:sup>\n ) accumulation (\n p<\/jats:italic>\n < 0.01).\n In vivo<\/jats:italic>\n , erastin accelerated LN progression, whereas Fer-1 significantly reduced proteinuria, renal pathology, and inflammatory cytokines.\n <\/jats:p>\n <\/jats:sec>\n \n Innovation and Conclusion:<\/jats:title>\n \n The study provided direct evidence of ferroptosis markers in renal tissues of LN patients. RTECs exhibited the intrinsic abnormalities that trigger ferroptosis, greatly contributing to the progression of LN. Our findings highlighted the critical role of region-specific tubular ferroptosis in driving renal pathology. Early intervention targeting ferroptosis of RTECs in the renal cortex might be an effective strategy for treating LN.\n Antioxid. Redox Signal.<\/jats:italic>\n 44, 197\u2013212.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/15230864251396446","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T03:07:24Z","timestamp":1763435244000},"page":"197-212","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Ferroptosis in Tubular Epithelial Cells Across Distinct Renal Regions Is a Primary Causal Factor for Lupus Nephritis"],"prefix":"10.1177","volume":"44","author":[{"given":"Wumeng","family":"Jin","sequence":"first","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualing","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofen","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanming","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanqun","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Du","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengping","family":"Wen","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changfeng","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.109213"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214819"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2024.01.001"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.1139\/o59-099"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.08.013"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00243.2006"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.14670\/hh-29.10.553"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.03.012"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2239"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(19)30237-5"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123378"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104215"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-010-8207-1"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05969-9"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3595"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(24)00398-2"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.578952"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-042222-025000"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11030142"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.04.030"},{"key":"e_1_3_4_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.12.006"},{"key":"e_1_3_4_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.11.006"},{"key":"e_1_3_4_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00993-3"},{"key":"e_1_3_4_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-07185-5"},{"key":"e_1_3_4_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114537"},{"key":"e_1_3_4_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1989.184"},{"key":"e_1_3_4_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00722-z"},{"key":"e_1_3_4_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110181"},{"key":"e_1_3_4_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-021-01663-3"},{"key":"e_1_3_4_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.11.012"},{"key":"e_1_3_4_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/bor.0000000000000089"},{"key":"e_1_3_4_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.01.025"},{"key":"e_1_3_4_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43308-w"},{"key":"e_1_3_4_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.2315"},{"key":"e_1_3_4_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.021"},{"key":"e_1_3_4_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.06.005"},{"issue":"10","key":"e_1_3_4_39_1","first-page":"1934","article-title":"The Systemic Lupus Activity Measure-revised, the Mexican Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and a modified SLEDAI-2K are adequate instruments to measure disease activity in systemic lupus erythematosus","volume":"31","author":"Uribe AG","year":"2004","unstructured":"Uribe AG, , Vil\u00e1 LM, , McGwin GJr, et al. The Systemic Lupus Activity Measure-revised, the Mexican Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and a modified SLEDAI-2K are adequate instruments to measure disease activity in systemic lupus erythematosus. J Rheumatol, 2004; 31(10):1934\u20131940.","journal-title":"J Rheumatol"},{"key":"e_1_3_4_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27107-8"},{"key":"e_1_3_4_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4012"},{"key":"e_1_3_4_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2014-204830"},{"key":"e_1_3_4_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-023-03476-6"},{"key":"e_1_3_4_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac300695p"},{"key":"e_1_3_4_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/09612033221102076"},{"key":"e_1_3_4_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-017-2066-y"},{"key":"e_1_3_4_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2024.149009"},{"key":"e_1_3_4_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00360.2018"},{"key":"e_1_3_4_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac900241u"},{"key":"e_1_3_4_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01254-x"},{"key":"e_1_3_4_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010"},{"key":"e_1_3_4_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155195"},{"key":"e_1_3_4_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102939"},{"key":"e_1_3_4_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112886"}],"container-title":["Antioxidants & Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15230864251396446","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15230864251396446","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15230864251396446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:56:20Z","timestamp":1777377380000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15230864251396446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":53,"journal-issue":{"issue":"4-6","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1177\/15230864251396446"],"URL":"https:\/\/doi.org\/10.1177\/15230864251396446","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]}}}