{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:08:10Z","timestamp":1780510090589,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The progression of acute kidney injury (AKI) to chronic kidney disease (CKD) represents a unique renal disease scenario, yet its exact mechanisms remain unclear. The transport of renal metabolic byproducts plays a crucial role in maintaining systemic homeostasis and the repair process. The glutathione\u2010based lipid oxidation\u2013reduction system is essential for preserving cellular function. However, the relationship between the disruption of the redox system during the AKI\u2010CKD transition and renal transport proteins remains unclear. We investigated the mechanisms by which the transport protein multidrug resistance\u2010associated protein 1 (MRP1) mediates the destruction of the redox system during renal ischemia\u2010reperfusion injury (IRI) and devised interventions related to renal ferroptosis. Transcriptome analysis and a unilateral kidney IRI model were employed to explore changes in MRP1 expression during the AKI\u2010CKD process. Functional experiments simulating in vivo renal IRI were conducted using Carbonyl Cyanide m\u2010Chlorophenylhydrazine (CCCP)\u2010treated renal tubular epithelial cells. MK571(MRP1 inhibitor) and Fer\u20101 were used to inhibit MRP1 and ferroptosis, respectively. Kidney tissue damage and fibrosis area were evaluated using staining methods like KIM1 and Masson. In the renal IRI model, upregulation of the transport protein MRP1 expression in renal tissue was observed. MRP1 is responsible for transporting glutathione outside the cell. MK571 significantly inhibited the AKI\u2010 CKD transition and immune cell infiltration. Both the deletion or inhibition of MRP1 can also alleviate ferroptosis. However, the combined use of MK571 and Fer\u20101 did not show additional kidney protective effects. Elevated expression of the renal transport protein MRP1 during renal IRI induces the extracellular leakage of glutathione, leading to ferroptosis. Inhibiting MRP1 can slow down renal ferroptosis and the progression from AKI\u2010CKD.<\/jats:p>","DOI":"10.1002\/jcp.70105","type":"journal-article","created":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T08:39:08Z","timestamp":1761467948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multidrug Resistance\u2010Associated Protein 1 Aberration\u2010Incurred Glutathione Efflux Drives Renal Ferroptosis and Acute Kidney Injury\u2010Chronic Kidney Disease Progression"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9370-0746","authenticated-orcid":false,"given":"Juan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Lanzhou University, The First Clinical Medical College Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1342-1592","authenticated-orcid":false,"given":"Haiqian","family":"An","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Hospital of Lanzhou University, The First Clinical Medical College Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8477-9769","authenticated-orcid":false,"given":"Sen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Hospital of Lanzhou University, The First Clinical Medical College Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0395-3993","authenticated-orcid":false,"given":"Yufeng","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-382X","authenticated-orcid":false,"given":"Lang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Hospital of Lanzhou University, The First Clinical Medical College Lanzhou University Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022630299"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02196"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.086579"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molp.2023.09.010"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.637162"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9040426"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101576"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.310409"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1139\/y89-004"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-020-00793-2"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8090413"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167433"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94716"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103340"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015121376"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-011112-140317"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3283581a64"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215303"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(03)00504-5"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11243951"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06247-4"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103500"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-022-02277-5"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-00931-8"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2023.5313"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2013.12.041"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102999"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102939"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111347"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.70105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:22:52Z","timestamp":1761672172000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.70105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/jcp.70105"],"URL":"https:\/\/doi.org\/10.1002\/jcp.70105","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70105"}}