{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:43:41Z","timestamp":1791924221743,"version":"4.3.4"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81673510"],"award-info":[{"award-number":["No. 81673510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073936"],"award-info":[{"award-number":["82073936"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Outstanding Scientific Fund of Shengjing Hospital","award":["No. M0779"],"award-info":[{"award-number":["No. M0779"]}]},{"name":"Joint Funds for the Innovation of Science and Technology of Fujian Province","award":["No. 2021Y9038"],"award-info":[{"award-number":["No. 2021Y9038"]}]},{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["No. 2025GGA015"],"award-info":[{"award-number":["No. 2025GGA015"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch. Pharm. Res."],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1007\/s12272-026-01599-9","type":"journal-article","created":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T15:10:14Z","timestamp":1771773014000},"page":"223-241","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["JAK2\/STAT3-dependent regulation of MDM4\/MDM2-p53 signaling in methotrexate-induced ferroptosis and nephrotoxicity"],"prefix":"10.1007","volume":"49","author":[{"given":"Yu","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maobai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8573-8028","authenticated-orcid":false,"given":"Limei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"issue":"5","key":"1599_CR1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41581-023-00689-x","volume":"19","author":"H Bay\u0131r","year":"2023","unstructured":"Bay\u0131r H, Dixon SJ, Tyurina YY, Kellum JA, Kagan VE (2023) Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney. Nat Rev Nephrol 19(5):315\u2013336. https:\/\/doi.org\/10.1038\/s41581-023-00689-x","journal-title":"Nat Rev Nephrol"},{"issue":"2","key":"1599_CR2","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1124\/pr.119.018440","volume":"72","author":"U Bharadwaj","year":"2020","unstructured":"Bharadwaj U, Kasembeli MM, Robinson P, Tweardy DJ (2020) Targeting janus kinases and signal transducer and activator of transcription 3 to treat inflammation, fibrosis, and cancer: rationale, progress, and caution. Pharmacol Rev 72(2):486\u2013526. https:\/\/doi.org\/10.1124\/pr.119.018440","journal-title":"Pharmacol Rev"},{"issue":"6","key":"1599_CR4","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210518","volume":"218","author":"X Chen","year":"2021","unstructured":"Chen X, Kang R, Kroemer G, Tang D (2021) Ferroptosis in infection, inflammation, and immunity. J Exp Med 218(6):e20210518. https:\/\/doi.org\/10.1084\/jem.20210518","journal-title":"J Exp Med"},{"issue":"3","key":"1599_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05716-0","volume":"14","author":"Y Chen","year":"2023","unstructured":"Chen Y, Fang ZM, Yi X, Wei X, Jiang DS (2023) The interaction between ferroptosis and inflammatory signaling pathways. Cell Death Dis 14(3):205. https:\/\/doi.org\/10.1038\/s41419-023-05716-0","journal-title":"Cell Death Dis"},{"issue":"10","key":"1599_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30578","volume":"70","author":"Y Cheng","year":"2023","unstructured":"Cheng Y, Chen Y, Zhao M, Wang M, Liu M, Zhao L (2023) Metabolomic profiling reveals the mechanisms underlying the nephrotoxicity of methotrexate in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 70(10):e30578. https:\/\/doi.org\/10.1002\/pbc.30578","journal-title":"Pediatr Blood Cancer"},{"key":"1599_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116227","volume":"307","author":"J Dong","year":"2023","unstructured":"Dong J, Du C, Xu C, Wang Q, Wang Z, Zhu Q, Lv X, Zhang L, Li J, Huang C, Wang H, Ma T (2023) Verbenalin attenuates hepatic damage and mitochondrial dysfunction in alcohol-associated steatohepatitis by regulating MDMX\/PPAR\u03b1-mediated ferroptosis. J Ethnopharmacol 307:116227. https:\/\/doi.org\/10.1016\/j.jep.2023.116227","journal-title":"J Ethnopharmacol"},{"issue":"1","key":"1599_CR8","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/jmcb\/mjx005","volume":"9","author":"S El-Dahr","year":"2017","unstructured":"El-Dahr S, Hilliard S, Saifudeen Z (2017) Regulation of kidney development by the Mdm2\/Mdm4-p53 axis. J Mol Cell Biol 9(1):26\u201333. https:\/\/doi.org\/10.1093\/jmcb\/mjx005","journal-title":"J Mol Cell Biol"},{"issue":"3","key":"1599_CR9","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1002\/ar.24482","volume":"304","author":"RA Elmansy","year":"2021","unstructured":"Elmansy RA, Seleem HS, Mahmoud AR, Hassanein EHM, Ali FEM (2021) Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study. Anat Rec (Hoboken) 304(3):647\u2013661. https:\/\/doi.org\/10.1002\/ar.24482","journal-title":"Anat Rec (Hoboken)"},{"key":"1599_CR10","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/859383","volume":"2015","author":"AA El-Sheikh","year":"2015","unstructured":"El-Sheikh AA, Morsy MA, Abdalla AM, Hamouda AH, Alhaider IA (2015) Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediators Inflamm 2015:859383. https:\/\/doi.org\/10.1155\/2015\/859383","journal-title":"Mediators Inflamm"},{"issue":"23","key":"1599_CR12","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1056\/nejm194806032382301","volume":"238","author":"S Farber","year":"1948","unstructured":"Farber S, Diamond LK (1948) Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med 238(23):787\u2013793. https:\/\/doi.org\/10.1056\/nejm194806032382301","journal-title":"N Engl J Med"},{"issue":"11","key":"1599_CR14","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1038\/nrm2996","volume":"11","author":"MC Frame","year":"2010","unstructured":"Frame MC, Patel H, Serrels B, Lietha D, Eck MJ (2010) The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol 11(11):802\u2013814. https:\/\/doi.org\/10.1038\/nrm2996","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"1599_CR15","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.3324\/haematol.2023.283613","volume":"109","author":"L Gasparoli","year":"2024","unstructured":"Gasparoli L, Virely C, Tsakaneli A, Che N, Edwards D, Bartram J, Hubank M, Pal D, Heidenreich O, Martens JHA, De Boer J, Williams O (2024) Susceptibility of pediatric acute lymphoblastic leukemia to STAT3 inhibition depends on p53 induction. Haematologica 109(4):1069\u20131081. https:\/\/doi.org\/10.3324\/haematol.2023.283613","journal-title":"Haematologica"},{"issue":"9","key":"1599_CR16","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.29518","volume":"14","author":"KM Hamed","year":"2022","unstructured":"Hamed KM, Dighriri IM, Baomar AF, Alharthy BT, Alenazi FE, Alali GH, Alenazy RH, Alhumaidi NT, Alhulayfi DH, Alotaibi YB, Alhumaidan SS, Alhaddad ZA, Humadi AA, Alzahrani SA, Alobaid RH (2022) Overview of methotrexate toxicity: a comprehensive literature review. Cureus 14(9):e29518. https:\/\/doi.org\/10.7759\/cureus.29518","journal-title":"Cureus"},{"issue":"4","key":"1599_CR17","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s12272-023-01436-3","volume":"46","author":"EHM Hassanein","year":"2023","unstructured":"Hassanein EHM, Sayed AM, El-Ghafar OAMA, Omar ZMM, Rashwan EK, Mohammedsaleh ZM, Kyung SY, Park JH, Kim HS, Ali FEM (2023) Apocynin abrogates methotrexate-induced nephrotoxicity: role of TLR4\/NF-\u03baB-p65\/p38-MAPK, IL-6\/STAT-3, PPAR-\u03b3, and SIRT1\/FOXO3 signaling pathways. Arch Pharm Res 46(4):339\u2013359. https:\/\/doi.org\/10.1007\/s12272-023-01436-3","journal-title":"Arch Pharm Res"},{"key":"1599_CR18","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.biopha.2018.08.050","volume":"107","author":"R Heidari","year":"2018","unstructured":"Heidari R, Ahmadi A, Mohammadi H, Ommati MM, Azarpira N, Niknahad H (2018) Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance. Biomed Pharmacother 107:834\u2013840. https:\/\/doi.org\/10.1016\/j.biopha.2018.08.050","journal-title":"Biomed Pharmacother"},{"issue":"12","key":"1599_CR19","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1634\/theoncologist.2015-0164","volume":"21","author":"SC Howard","year":"2016","unstructured":"Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD (2016) Preventing and managing toxicities of high-dose methotrexate. Oncologist 21(12):1471\u20131482. https:\/\/doi.org\/10.1634\/theoncologist.2015-0164","journal-title":"Oncologist"},{"issue":"1","key":"1599_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2256-z","volume":"11","author":"Z Hu","year":"2020","unstructured":"Hu Z, Zhang H, Yi B, Yang S, Liu J, Hu J, Wang J, Cao K, Zhang W (2020) VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis. Cell Death Dis 11(1):73. https:\/\/doi.org\/10.1038\/s41419-020-2256-z","journal-title":"Cell Death Dis"},{"key":"1599_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115677","volume":"259","author":"C Hu","year":"2023","unstructured":"Hu C, Zhang B, Zhao S (2023) METTL3-mediated N6-methyladenosine modification stimulates mitochondrial damage and ferroptosis of kidney tubular epithelial cells following acute kidney injury by modulating the stabilization of MDM2-p53-LMNB1 axis. Eur J Med Chem 259:115677. https:\/\/doi.org\/10.1016\/j.ejmech.2023.115677","journal-title":"Eur J Med Chem"},{"issue":"3","key":"1599_CR22","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s10863-024-10015-0","volume":"56","author":"F Huang","year":"2024","unstructured":"Huang F, Wang Y, Lv X, Huang C (2024) WTAP-mediated N6-methyladenosine modification promotes the inflammation, mitochondrial damage and ferroptosis of kidney tubular epithelial cells in acute kidney injury by regulating LMNB1 expression and activating NF-\u03baB and JAK2\/STAT3 pathways. J Bioenerg Biomembr 56(3):285\u2013296. https:\/\/doi.org\/10.1007\/s10863-024-10015-0","journal-title":"J Bioenerg Biomembr"},{"issue":"1","key":"1599_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01841-1","volume":"22","author":"SH Lee","year":"2024","unstructured":"Lee SH, Kim KH, Lee SM, Park SJ, Lee S, Cha RH, Lee JW, Kim DK, Kim YS, Ye SK, Yang SH (2024) STAT3 blockade ameliorates LPS-induced kidney injury through macrophage-driven inflammation. Cell Commun Signal 22(1):476. https:\/\/doi.org\/10.1186\/s12964-024-01841-1","journal-title":"Cell Commun Signal"},{"issue":"2","key":"1599_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2298-2","volume":"11","author":"J Li","year":"2020","unstructured":"Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, Sun B, Wang G (2020) Ferroptosis: past, present and future. Cell Death Dis 11(2):88. https:\/\/doi.org\/10.1038\/s41419-020-2298-2","journal-title":"Cell Death Dis"},{"key":"1599_CR26","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.1016459","volume":"9","author":"Y Li","year":"2022","unstructured":"Li Y, Du Y, Zhang Y, Chen C, Zhang J, Zhang X, Zhang M, Yan Y (2022) Machine learning algorithm-based identification and verification of characteristic genes in acute kidney injury. Front Med (Lausanne) 9:1016459. https:\/\/doi.org\/10.3389\/fmed.2022.1016459","journal-title":"Front Med (Lausanne)"},{"issue":"3","key":"1599_CR27","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1074\/jbc.M109.064212","volume":"285","author":"ST Lim","year":"2010","unstructured":"Lim ST, Miller NL, Nam JO, Chen XL, Lim Y, Schlaepfer DD (2010) Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival. J Biol Chem 285(3):1743\u20131753. https:\/\/doi.org\/10.1074\/jbc.M109.064212","journal-title":"J Biol Chem"},{"issue":"2","key":"1599_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166968","volume":"1870","author":"G Lin","year":"2024","unstructured":"Lin G, Jiang H, Zhang Z, Ning L, Zhang W, Peng L, Xu S, Sun W, Tao S, Zhang T, Tang L (2024) Molecular mechanism of NR4A1\/MDM2\/P53 signaling pathway regulation inducing ferroptosis in renal tubular epithelial cells involved in the progression of renal ischemia-reperfusion injury. Biochim Et Biophysica Acta (BBA)-Molecular Basis Dis 1870(2):166968. https:\/\/doi.org\/10.1016\/j.bbadis.2023.166968","journal-title":"Biochim Et Biophysica Acta (BBA)-Molecular Basis Dis"},{"issue":"47","key":"1599_CR29","doi-asserted-by":"publisher","first-page":"16836","DOI":"10.1073\/pnas.1415518111","volume":"111","author":"A Linkermann","year":"2014","unstructured":"Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C, De Zen F, Prokai A, Zuchtriegel G, Krombach F, Welz PS, Weinlich R, Vanden Berghe T, Vandenabeele P, Pasparakis M, Bleich M, Weinberg JM, Reichel CA, Br\u00e4sen JH, Kunzendorf U, Anders HJ, Stockwell BR, Green DR, Krautwald S (2014) Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci U S A 111(47):16836\u201316841. https:\/\/doi.org\/10.1073\/pnas.1415518111","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"13","key":"1599_CR31","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-845","volume":"10","author":"B Liu","year":"2022","unstructured":"Liu B, Ao S, Tan F, Ma W, Liu H, Liang H, Yang X, Chi X (2022) Transcriptomic analysis and laboratory experiments reveal potential critical genes and regulatory mechanisms in sepsis-associated acute kidney injury. Ann Transl Med 10(13):737. https:\/\/doi.org\/10.21037\/atm-22-845","journal-title":"Ann Transl Med"},{"key":"1599_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1233259","volume":"11","author":"Y Liu","year":"2023","unstructured":"Liu Y, Wang W, Zhang J, Gao S, Xu T, Yin Y (2023) JAK\/STAT signaling in diabetic kidney disease. Front Cell Dev Biol 11:1233259. https:\/\/doi.org\/10.3389\/fcell.2023.1233259","journal-title":"Front Cell Dev Biol"},{"issue":"9","key":"1599_CR33","doi-asserted-by":"publisher","first-page":"5258","DOI":"10.1074\/jbc.M707125200","volume":"283","author":"X Lu","year":"2008","unstructured":"Lu X, Huang LJ, Lodish HF (2008) Dimerization by a cytokine receptor is necessary for constitutive activation of JAK2V617F. J Biol Chem 283(9):5258\u20135266. https:\/\/doi.org\/10.1074\/jbc.M707125200","journal-title":"J Biol Chem"},{"issue":"7","key":"1599_CR34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0307472","volume":"19","author":"G Luo","year":"2024","unstructured":"Luo G, Gao Y, Zheng Z, Gao B, Wang L, Tang X, Lei C (2024) Exploring the role of ferroptosis-related genes as biomarkers in acute kidney injury. PLoS ONE 19(7):e0307472. https:\/\/doi.org\/10.1371\/journal.pone.0307472","journal-title":"PLoS ONE"},{"key":"1599_CR67","doi-asserted-by":"publisher","unstructured":"Mahoutforoush A, Asadollahi L, Hamishehkar H, Abbaspour-Ravasjani S, Solouk A, Haghbin Nazarpak M (2023) Targeted delivery of pennyroyal via methotrexate functionalized PEGylated nanostructured lipid carriers into breast cancer cells; A multiple pathways apoptosis activator. Adv Pharm Bull 13(4):747\u2013760. https:\/\/doi.org\/10.34172\/apb.2023.077","DOI":"10.34172\/apb.2023.077"},{"issue":"6","key":"1599_CR35","doi-asserted-by":"publisher","first-page":"4699","DOI":"10.1007\/s11033-020-05481-9","volume":"47","author":"V Maksimovic","year":"2020","unstructured":"Maksimovic V, Pavlovic-Popovic Z, Vukmirovic S, Cvejic J, Mooranian A, Al-Salami H, Mikov M, Golocorbin-Kon S (2020) Molecular mechanism of action and pharmacokinetic properties of methotrexate. Mol Biol Rep 47(6):4699\u20134708. https:\/\/doi.org\/10.1007\/s11033-020-05481-9","journal-title":"Mol Biol Rep"},{"issue":"4","key":"1599_CR36","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.nefro.2020.03.005","volume":"40","author":"D Martin-Sanchez","year":"2020","unstructured":"Martin-Sanchez D, Fontecha-Barriuso M, Martinez-Moreno JM, Ramos AM, Sanchez-Ni\u00f1o MD, Guerrero-Hue M, Moreno JA, Ortiz A, Sanz AB (2020) Ferroptosis and kidney disease. Nefrologia 40(4):384\u2013394. https:\/\/doi.org\/10.1016\/j.nefro.2020.03.005","journal-title":"Nefrologia"},{"issue":"5","key":"1599_CR38","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1158\/1541-7786.mcr-12-0528","volume":"11","author":"BC McFarland","year":"2013","unstructured":"McFarland BC, Gray GK, Nozell SE, Hong SW, Benveniste EN (2013) Activation of the NF-\u03baB pathway by the STAT3 inhibitor JSI-124 in human glioblastoma cells. Mol Cancer Res 11(5):494\u2013505. https:\/\/doi.org\/10.1158\/1541-7786.mcr-12-0528","journal-title":"Mol Cancer Res"},{"key":"1599_CR66","doi-asserted-by":"publisher","unstructured":"Niu X, Wang C, Li H, Chen W (2024) Role of OPG\/RANKL\/RANK\/TLR4 signaling pathway in sepsis-associated acute kidney injury. BMC Nephrol 25(1):205. https:\/\/doi.org\/10.1186\/s12882-024-03648-1","DOI":"10.1186\/s12882-024-03648-1"},{"issue":"8","key":"1599_CR41","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1002\/ijc.30214","volume":"139","author":"Z Pan","year":"2016","unstructured":"Pan Z, Yang G, He H, Zhao G, Yuan T, Li Y, Shi W, Gao P, Dong L, Li Y (2016) Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: a prospective and single-arm study. Int J Cancer 139(8):1864\u20131872. https:\/\/doi.org\/10.1002\/ijc.30214","journal-title":"Int J Cancer"},{"issue":"3","key":"1599_CR42","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/ki.2010.154","volume":"78","author":"M Pang","year":"2010","unstructured":"Pang M, Ma L, Gong R, Tolbert E, Mao H, Ponnusamy M, Chin YE, Yan H, Dworkin LD, Zhuang S (2010) A novel STAT3 inhibitor, S3I\u2013201, attenuates renal interstitial fibroblast activation and interstitial fibrosis in obstructive nephropathy. Kidney Int 78(3):257\u2013268. https:\/\/doi.org\/10.1038\/ki.2010.154","journal-title":"Kidney Int"},{"issue":"5","key":"1599_CR43","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1159\/000368528","volume":"40","author":"N Panizo","year":"2015","unstructured":"Panizo N, Rubio-Navarro A, Amaro-Villalobos JM, Egido J, Moreno JA (2015) Molecular mechanisms and novel therapeutic approaches to rhabdomyolysis-induced acute kidney injury. Kidney Blood Press Res 40(5):520\u2013532. https:\/\/doi.org\/10.1159\/000368528","journal-title":"Kidney Blood Press Res"},{"issue":"6","key":"1599_CR44","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1097\/mcc.0000000000000653","volume":"25","author":"MA Perazella","year":"2019","unstructured":"Perazella MA (2019) Drug-induced acute kidney injury: diverse mechanisms of tubular injury. Curr Opin Crit Care 25(6):550\u2013557. https:\/\/doi.org\/10.1097\/mcc.0000000000000653","journal-title":"Curr Opin Crit Care"},{"issue":"6","key":"1599_CR46","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1080\/01913123.2022.2154877","volume":"46","author":"AM Shalaby","year":"2022","unstructured":"Shalaby AM, Albakoush KMM, Alabiad MA, Alorini M, Jaber FA, Elkholy MR, Tawfeek SE (2022) Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat. Ultrastruct Pathol 46(6):531\u2013541. https:\/\/doi.org\/10.1080\/01913123.2022.2154877","journal-title":"Ultrastruct Pathol"},{"issue":"19","key":"1599_CR47","doi-asserted-by":"publisher","first-page":"5349","DOI":"10.1002\/j.1460-2075.1996.tb00919.x","volume":"15","author":"A Shvarts","year":"1996","unstructured":"Shvarts A, Steegenga WT, Riteco N, van Laar T, Dekker P, Bazuine M, van Ham RC, van der Houven Oordt W, Hateboer G, van der Eb AJ, Jochemsen AG (1996) MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J 15(19):5349\u20135357","journal-title":"EMBO J"},{"key":"1599_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110108","volume":"127","author":"Y Sun","year":"2020","unstructured":"Sun Y, Chen P, Zhai B, Zhang M, Xiang Y, Fang J, Xu S, Gao Y, Chen X, Sui X, Li G (2020) The emerging role of ferroptosis in inflammation. Biomed Pharmacother 127:110108. https:\/\/doi.org\/10.1016\/j.biopha.2020.110108","journal-title":"Biomed Pharmacother"},{"issue":"7\u20138","key":"1599_CR50","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1101\/gad.334219.119","volume":"34","author":"D Venkatesh","year":"2020","unstructured":"Venkatesh D, O\u2019Brien NA, Zandkarimi F, Tong DR, Stokes ME, Dunn DE, Kengmana ES, Aron AT, Klein AM, Csuka JM, Moon SH, Conrad M, Chang CJ, Lo DC, D\u2019Alessandro A, Prives C, Stockwell BR (2020) MDM2 and MDMX promote ferroptosis by PPAR\u03b1-mediated lipid remodeling. Genes Dev 34(7\u20138):526\u2013543. https:\/\/doi.org\/10.1101\/gad.334219.119","journal-title":"Genes Dev"},{"issue":"1","key":"1599_CR52","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jphs.2021.02.007","volume":"146","author":"X Wei","year":"2021","unstructured":"Wei X, Wu Y, Tang H, Wang B, Wang Y, Sun W, Asenso J, Xiao F, Wang C (2021) CP-25 ameliorates methotrexate induced nephrotoxicity via improving renal apoptosis and methotrexate excretion. J Pharmacol Sci 146(1):21\u201328. https:\/\/doi.org\/10.1016\/j.jphs.2021.02.007","journal-title":"J Pharmacol Sci"},{"issue":"3","key":"1599_CR53","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1177\/1078155215594417","volume":"22","author":"T Wiczer","year":"2016","unstructured":"Wiczer T, Dotson E, Tuten A, Phillips G, Maddocks K (2016) Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity. J Oncol Pharm Pract 22(3):430\u2013436. https:\/\/doi.org\/10.1177\/1078155215594417","journal-title":"J Oncol Pharm Pract"},{"issue":"6","key":"1599_CR54","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1634\/theoncologist.11-6-694","volume":"11","author":"BC Widemann","year":"2006","unstructured":"Widemann BC, Adamson PC (2006) Understanding and managing methotrexate nephrotoxicity. Oncologist 11(6):694\u2013703. https:\/\/doi.org\/10.1634\/theoncologist.11-6-694","journal-title":"Oncologist"},{"issue":"10","key":"1599_CR55","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1002\/cncr.20255","volume":"100","author":"BC Widemann","year":"2004","unstructured":"Widemann BC, Balis FM, Kempf-Bielack B, Bielack S, Pratt CB, Ferrari S, Bacci G, Craft AW, Adamson PC (2004) High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer 100(10):2222\u20132232. https:\/\/doi.org\/10.1002\/cncr.20255","journal-title":"Cancer"},{"issue":"9","key":"1599_CR56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006275","volume":"12","author":"LH Wong","year":"2016","unstructured":"Wong LH, Sinha S, Bergeron JR, Mellor JC, Giaever G, Flaherty P, Nislow C (2016) Reverse chemical genetics: comprehensive fitness profiling reveals the spectrum of drug target interactions. PLoS Genet 12(9):e1006275. https:\/\/doi.org\/10.1371\/journal.pgen.1006275","journal-title":"PLoS Genet"},{"key":"1599_CR57","doi-asserted-by":"publisher","DOI":"10.1590\/acb381023","volume":"38","author":"Y Xiong","year":"2023","unstructured":"Xiong Y, Jian J, Yu H, Wu J, Mao H, Feng R, Wang L, Jian Y, Liu X (2023) Cyanidin-3-O-glucoside plays a protective role against renal ischemia\/ reperfusion injury via the JAK\/STAT pathway. Acta Cir Bras 38:e381023. https:\/\/doi.org\/10.1590\/acb381023","journal-title":"Acta Cir Bras"},{"issue":"1","key":"1599_CR58","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4103\/ejpi.ejpi-d-23-00027","volume":"67","author":"S Xu","year":"2024","unstructured":"Xu S, Luo J, Wang Y, Chen X (2024) Fatty acid binding protein-4 silencing inhibits ferroptosis to alleviate lipopolysaccharide-induced injury of renal tubular epithelial cells by blocking janus kinase 2\/signal transducer and activator of transcription 3 signaling. J Physiol Invest 67(1):47\u201356. https:\/\/doi.org\/10.4103\/ejpi.ejpi-d-23-00027","journal-title":"J Physiol Invest"},{"issue":"1","key":"1599_CR59","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1093\/ndt\/gfm509","volume":"23","author":"N Yang","year":"2008","unstructured":"Yang N, Luo M, Li R, Huang Y, Zhang R, Wu Q, Wang F, Li Y, Yu X (2008) Blockage of JAK\/STAT signalling attenuates renal ischaemia-reperfusion injury in rat. Nephrol Dial Transplant 23(1):91\u2013100. https:\/\/doi.org\/10.1093\/ndt\/gfm509","journal-title":"Nephrol Dial Transplant"},{"issue":"10002","key":"1599_CR60","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1016\/s0140-6736(15)00344-x","volume":"386","author":"L Yang","year":"2015","unstructured":"Yang L, Xing G, Wang L, Wu Y, Li S, Xu G, He Q, Chen J, Chen M, Liu X, Zhu Z, Yang L, Lian X, Ding F, Li Y, Wang H, Wang J, Wang R, Mei C, Xu J, Li R, Cao J, Zhang L, Wang Y, Xu J, Bao B, Liu B, Chen H, Li S, Zha Y, Luo Q, Chen D, Shen Y, Liao Y, Zhang Z, Wang X, Zhang K, Liu L, Mao P, Guo C, Li J, Wang Z, Bai S, Shi S, Wang Y, Wang J, Liu Z, Wang F, Huang D, Wang S, Ge S, Shen Q, Zhang P, Wu L, Pan M, Zou X, Zhu P, Zhao J, Zhou M, Yang L, Hu W, Wang J, Liu B, Zhang T, Han J, Wen T, Zhao M, Wang H (2015) Acute kidney injury in China: a cross-sectional survey. Lancet 386(10002):1465\u20131471. https:\/\/doi.org\/10.1016\/s0140-6736(15)00344-x","journal-title":"Lancet"},{"issue":"5","key":"1599_CR61","doi-asserted-by":"publisher","DOI":"10.3892\/or.2022.8308","volume":"47","author":"X Yu","year":"2022","unstructured":"Yu X, Zhu D, Luo B, Kou W, Cheng Y, Zhu Y (2022) IFN\u03b3 enhances ferroptosis by increasing JAK\u2011STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma. Oncol Rep 47(5):97. https:\/\/doi.org\/10.3892\/or.2022.8308","journal-title":"Oncol Rep"},{"key":"1599_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122476","volume":"341","author":"C Yu","year":"2024","unstructured":"Yu C, Zhang J, Pei J, Luo J, Hong Y, Tian X, Liu Z, Zhu C, Long C, Shen L, He X, Wen S, Liu X, Wu S, Hua Y, Wei G (2024) IL-13 alleviates acute kidney injury and promotes regeneration via activating the JAK-STAT signaling pathway in a rat kidney transplantation model. Life Sci 341:122476. https:\/\/doi.org\/10.1016\/j.lfs.2024.122476","journal-title":"Life Sci"},{"issue":"9","key":"1599_CR63","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1007\/s00011-019-01258-4","volume":"68","author":"L Zhang","year":"2019","unstructured":"Zhang L, Lu P, Guo X, Liu T, Luo X, Zhu YT (2019) Inhibition of JAK2\/STAT3 signaling pathway protects mice from the DDP-induced acute kidney injury in lung cancer. Inflamm Res 68(9):751\u2013760. https:\/\/doi.org\/10.1007\/s00011-019-01258-4","journal-title":"Inflamm Res"},{"key":"1599_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113074","volume":"150","author":"Z Zhao","year":"2022","unstructured":"Zhao Z, Hua Z, Luo X, Li Y, Yu L, Li M, Lu C, Zhao T, Liu Y (2022) Application and pharmacological mechanism of methotrexate in rheumatoid arthritis. Biomed Pharmacother 150:113074. https:\/\/doi.org\/10.1016\/j.biopha.2022.113074","journal-title":"Biomed Pharmacother"},{"issue":"D1","key":"1599_CR65","doi-asserted-by":"publisher","first-page":"D571","DOI":"10.1093\/nar\/gkac935","volume":"51","author":"N Zhou","year":"2023","unstructured":"Zhou N, Yuan X, Du Q, Zhang Z, Shi X, Bao J, Ning Y, Peng L (2023) FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations. Nucleic Acids Res 51(D1):D571-d582. https:\/\/doi.org\/10.1093\/nar\/gkac935","journal-title":"Nucleic Acids Res"}],"container-title":["Archives of Pharmacal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12272-026-01599-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12272-026-01599-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12272-026-01599-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:37:38Z","timestamp":1773815858000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12272-026-01599-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":56,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["1599"],"URL":"https:\/\/doi.org\/10.1007\/s12272-026-01599-9","relation":{},"ISSN":["0253-6269","1976-3786"],"issn-type":[{"value":"0253-6269","type":"print"},{"value":"1976-3786","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"7 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}